Society for Mathematical Biology News

BMB Article Highlight: Weiming Wang et al. (2026)

Tue, 24 Mar 2026 20:12:05 GMT

Stochastic Modeling and Optimal Control of HIV-1 Infection Dynamics Under Combination Antiretroviral Therapy

by Yiping Tan, Suli Liu, Yongli Cai, Xiaodan Sun, Ruoxia Yao, Daihai He, Zhihang Peng, and Weiming Wang

Within-host HIV-1 dynamics under cART exhibit persistent fluctuations driven by environmental noise. We develop a stochastic differential equation model to show that this noise decisively influences viral suppression versus persistence. Through optimal control theory, we compare strategies of cART intensification, immune modulation, and their combination. A cART-dominated, immune-assisted approach proves most effective, ensuring rapid viral suppression and cost-efficiency. This study offers a theoretical framework for optimizing HIV-1 treatment protocols.

Stochastic Modeling and Optimal Control of HIV-1 Infection Dynamics Under Combination Antiretroviral Therapy

BMB Article Highlight: Ashley Scruse et al. (2026)

Tue, 17 Mar 2026 19:30:46 GMT

Counting Subnetworks Under Gene Duplication in Genetic Regulatory Networks

by Ashley Scruse, Jonathan Arnold, and Robert Robinson

Gene families help us understand how gene regulation evolves. While sequence evolution is well-studied, regulatory evolution is not. Members of gene families form genetic regulatory networks (GRNs) where gene A regulates gene B. We develop a model counting regulatory subnetwork motifs within gene families as they evolve through duplication. The result is a count |M(n)| of how these motifs evolve to a stage with n total genes. The key parameter is the probability that a regulatory relation is preserved when a gene is duplicated. For Full Duplication, the mean and variance of motif counts can be computed exactly, enabling significance tests to identify targets for directed evolution. Partial and Mixed Duplication models are also presented.

This graphical abstract illustrates the mathematical framework for counting subnetwork motifs in genetic regulatory networks (GRNs) under gene duplication. The left panel depicts the gene duplication process: before duplication, gene A regulates gene B; after duplication of B, the duplicate gene B' may inherit the regulatory relationship from A with probability π. The right panel presents the key analytical results for the Full Duplication model (π = 1), including closed-form expressions for the expected motif count E(|M|) and the second moment E(|M|²). The bottom section shows the statistical framework for identifying significant motifs, with formulas for variance and Z-score calculation, along with a workflow for applying these methods to identify targets for directed evolution. The paper also derives analogous results for Partial Duplication (0 ≤ π ≤ 1), where the inheritance probability vector π = (π₁, ..., πₖ) allows each gene family to have its own probability of inheriting regulatory relationships, and discusses the Mixed Duplication model, where with probability 1−q all regulatory links are retained and with probability q each link is retained independently with probability p. See the full article for these additional duplication models.

Biology in Numbers - Episode 3.4: Ranjini Bhattacharya

Tue, 24 Feb 2026 14:59:31 GMT

...where we talk forging cancer cells, science policy and dancing.

Ranjini is a final-year PhD student in the IMO Department at Moffitt Cancer Center. She uses evolutionary game theory to study cancer foraging. Outside of her research, Ranjini engages in science communication and science policy with non-expert audiences, and loves to engage her creative side.

You can connect with her on Linkedin.

Find out more about SMB on:

BMB Article Highlight: Xiunan Wang et al. (2026)

Wed, 18 Feb 2026 17:58:45 GMT

Immune Modulation in the Tumor Microenvironment: Bifurcation Analysis of Cancer-CTL-Monocyte Dynamics

by Eymard Hernandez-Lopez, Russell Milne, and Xiunan Wang.

Cancer remains a major global health challenge. To understand how tumors grow or are controlled by immunity, we develop a mathematical model describing interactions among cancer cells, cytotoxic T cells, and monocytes. The model captures two key features: monocyte-driven T cell stimulation and a threshold effect whereby very small tumors may fail to establish because of limited resources and immune pressure. By analyzing system dynamics, we identify three outcomes—tumor elimination, stable coexistence, or uncontrolled growth—and show how these depend on parameters that can be modified clinically. This framework helps predict which therapies are most likely to shift the system toward durable tumor control.

Immune Modulation in the Tumor Microenvironment

NEW!! SMB Annual Meeting Travel Grant

Robyn Araujo — Wed, 11 Feb 2026 21:20:35 GMT

SMB is pleased to announce need-based travel grants to the attend the ECMTB/SMB joint Annual Meeting in Graz, Austria this July. The travel grants aim to provide partial support and will be typically limited to $750 USD. The application deadline is 15 March 2026.

Details: https://smb.org/SMB-Annual-Meeting-Travel-Award

Online application form: https://smb.org/SMB-Annual-Meeting-Travel-Grant-Application/

BMB Article Highlight: Xia et al. (2026)

Fri, 06 Feb 2026 22:34:08 GMT

Defining optimal vaccine features for pandemic preparedness: An individual-based model bridging within- and between-host dynamics.

by Xia Y., Alexandre M., Thiébaut R, Maheu-Giroux M, and Prague M.

The Study Xia et al. 2026 highlights which vaccine feature can help stop the next "Disease X" respiratory pandemic before it spreads. Researchers developed a powerful simulation that links how viruses behave within-hosts to how they spread between-hosts. Technically, the model includes parameters like the antibody concentration needed for 50% protection, the effect on clinical outcome during infection and waning immunity. Results show that vaccines lasting longer and working at lower antibody levels are the most effective at cutting transmission. This work offers a roadmap for designing next-generation vaccines that could keep future outbreaks under control.

A framework to define optimal vaccine features for pandemic preparedness.

BMB Article Highlight: Kira Pugh et al. (2025)

Fri, 30 Jan 2026 21:48:08 GMT

A bibliometric study on mathematical oncology: interdisciplinarity, internationality, collaboration and trending topics

by Kira Pugh, Linnéa Gyllingberg, Stanislav Stratiev, and Sara Hamis

In this study, we use bibliometric methods to obtain a bird’s-eye view of mathematical oncology as a research field. Our data consist of articles from five leading mathematical biology journals (referred to as our focus journals), including the Bulletin of Mathematical Biology. We examine interdisciplinarity, internationality, and trending topics in the field. Our analysis reveals that, since the 1960s, mathematical oncology has become more interactive with external research fields and globally connected, with changes in research themes. Our results show that mathematical oncology benefits both the mathematical and life sciences. Insights from our study can be used to inform funding, teaching, organisation, and communication practices.

We investigate interdisciplinarity, internationality, and trending topics in mathematical oncology through discipline-based citation flows (left figure), global author connectivity (middle figure), and word frequencies in titles and abstracts (right figure).

Biology in Numbers - Episode 3.3: Reinhard Laubenbacher

Fri, 23 Jan 2026 16:30:55 GMT

AI or die - with Reinhard Laubenbacher

These days you can’t throw a stone without hitting some form of AI. Whether it’s to control your home sound system, or looking for a novel way to treat disease, we are still in the learning stages of how best to use these technologies.

So Biology in Numbers welcomes back Reinhard Laubenbacher, current SMB president, who talks about some uses in the field, its relevance in education, and why math biologists and the larger scientific community need to get ahead of AI to ensure it is incorporated into research in a meaningful way.

Here’s a useful and pretty primer for anyone completely new to AI: from the BBC. For those interested in that foundational paper by McCulloch and Pitts here’s the link: A logical calculus of the ideas immanent in nervous activity.

If you’d like to leave any suggestions for Reinhard on the subject, you can reach him at: Reinhard.Laubenbacher[at]medicine.ufl.edu

Find out more about SMB on:

Nominations now being accepted for officer positions on the SMB Board of Directors

Robyn Araujo — Tue, 20 Jan 2026 02:17:57 GMT

The Society is now accepting nominations for officer positions.These include the President-Elect, three regular members of the Board of Directors, one two-year and one four-year Early Career members of the Board. The latter are for those within five years of their PhD. Nominations are due by February 27, 2026.

Please email nominations (which could be self-nominations) to nominations@smb.org. These should include a 2-page CV and a brief election statement describing the nominee's past contributions and commitment to the SMB. Information regarding the duties of the Board and President-Elect can be found on the SMB web page, www.smb.org.

BMB Article Highlight: Rupleen Kaur et al. (2025)

Wed, 14 Jan 2026 16:26:50 GMT

Astrocyte Reprogramming Drives Tumor Progression and Chemotherapy Resistance in Agent-Based Models of Breast Cancer Brain Metastases

by Rupleen Kaur, Rowan Barker-Clarke, and Andrew Dhawan.

Patients with advanced cancer frequently develop brain metastases, resulting in poor survival rates and limited therapeutic options. Understanding the interactions between tumor cells and the brain microenvironment remains challenging. This project employs an agent-based model to demonstrate how brain-resident astrocytes, when reprogrammed by tumor cells, can enhance tumor growth and facilitate drug resistance. By simulating distinct brain regions and quantifying tumor morphology and treatment responses, the study shows how the local microenvironment influences tumor expansion and therapeutic outcomes.

Tumor cells reprogram brain-resident astrocytes from an anti-metastatic to a pro-metastatic phenotype. Agent-based modeling reveals that astrocyte density and distribution across distinct brain regions (A-C) determine tumor expansion and morphological complexity. High uniform density (B) increases lacunarity but decreases eccentricity, producing irregular yet circular tumors. Gradient distribution (C) drives directional expansion with high eccentricity and fractal complexity but reduced lacunarity. These microenvironment-dependent morphological phenotypes may influence tumor progression and treatment outcomes.

BMB Article Highlight: Ivo Siekmann. (2025)

Wed, 31 Dec 2025 19:47:10 GMT

Modelling ion channels with a view towards identifiability

by Ivo Siekmann.

Can we gain insight into the molecular structure of an ion channel from observing its opening and closing over time? Intuitively, we might expect that by mimicking the architecture of the channel in a model, the time scales of transitions between different biophysical states can be inferred from these observations. But on the one hand, many models are nonidentifiable which makes them unsuitable for mechanistic modelling of ion channels. On the other hand, models that represent completely different biophysical mechanisms can nevertheless be equivalent. Motivated by these challenges we suggest alternative approaches how opening and closing as well as biophysical dynamics of ion channels can be represented in mathematical models.

The fully-connected model is always non-identifiable model and therefore unsuitable for mechanistic modelling. But for some parameter sets it can be reduced to the models CCO or COC. CCO and COC are always equivalent although both represent different biophysical processes.

Autumn 2025 SMB Newsletter

Tue, 16 Dec 2025 13:05:18 GMT

Olivia Chu (Bryn Mawr College), Ryan Murphy (University of South Australia), Ananth Srinivas (LSU Health New Orleans), and Sara Hamis (Uppsala University).

News - updates from:
People - Interview with Professor Richard Bertram, Florida State University
Editorial - SMB Principles of Community and engaging with SMB
Featured Figure - Kit Gallagher, University of Oxford
In our next issue...

To see the subsections of this issue, click the links at the above items.

Contributing content

Issues of the newsletter are released four times per year in Spring, Summer, Autumn, and Winter. The newsletter serves the SMB community with news and updates, so please share it with your colleagues and contribute content to future issues.

We welcome submissions to expand the content of the newsletter. The next issue will be released in the Winter, so if you would like to contribute, please send an email to the editors by the start of February 2026 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the Member Forum rather than to the newsletter.

If you have any suggestions on how to improve the newsletter and would like to become more involved and/or contribute, please contact us at any time. We appreciate and welcome feedback and ideas from the community. The editors can be reached at newsletter@smb.org.

We hope you enjoy this issue of the newsletter!

Olivia, Ryan, Ananth, and Sara
Editors, SMB Newsletter

News Section

By Sara Hamis

In this issue of the News section, we highlight the updates from the Bulletin of Mathematical Biology (BMB), SMB Subgroups, and Royal Society Publishing. Read on below.

From BMB

Did you know that publishing in the Bulletin of Mathematical Biology (BMB) provides financial support to the SMB? Learn how in a recent editorial article, available here.

SMB Subgroup Updates

Formation of SMB Subgroup on Reaction Networks

Dear Colleagues,

We are excited to report that the Society for Mathematical Biology has approved the formation of a new Subgroup on Reaction Networks. This subgroup will bring together scientists from different areas studying the mathematics of reaction networks, both stochastic and deterministic, and including applications such as chemical reaction computing, cellular dynamics, and population level dynamics. The approval was the result of a petition signed by as many as 70 participants of the 2024 annual SMB conference in Seoul, Korea. We expect to organize satellite meetings and special sessions during annual SMB meetings, as well as collaborative workshops, virtual seminars and conferences, in addition to other initiatives.

At this early stage we are still finalizing the bylaws and delineating specific goals and activities of the new subgroup. We welcome all members of the community to participate, either by volunteering to serve in some capacity or simply by indicating their interest in the subgroup. Feel free to fill out the following survey, send us a line, or simply stay tuned for our inaugural set of activities at the 2026 SMB meeting in Graz, Austria.

Google Form link: https://forms.gle/qaDgSoPXhACSkKpx9

Best Regards,
Greg Rempala and Hye-Won Kang
Interim Co-Chairs

Immunobiology and Infection

The Immunobiology and Infection subgroup will be holding elections for the Chair and Secretary positions in the new year. Please keep an eye out for details about voting procedures and timelines. We are also launching a newsletter with research and workshop/conferences updates, and open positions shortly! More info to follow.

Cell & Developmental Biology (CDEV)

The CDEV Subgroup hosted a wonderful Job Market Webinar on November 6^th for students and postdocs who are preparing for the job market! The webinar was led by Anna Nelson (University of New Mexico) and Giulia Celora (University of Oxford), who both serve as SMB CDEV Subcommittee Members.
The CDEV Subgroup will be hosting a Virtual 3-min Research Session! Think three pages for a research statement is short? What about distilling your work into just three minutes with the help of a single slide? In Spring 2026, we invite researchers at all career stages to take on this CHALLENGE and join other members of the SMB CDEV community for a virtual gathering aimed at offering researchers a platform to share their scientific interests and vision in a friendly and informal setting. Presentations should be accessible to a non-specialist audience and highlight the broader significance of your work. Sign Up Here: https://forms.gle/FugESCrwYcocPazR7
The CDEV Subgroup will have a mini-symposium at the 2026 SMB/ESMTB Conference in Graz, Austria! Please be on the lookout for information on our speakers.
Follow our Blog: https://smb-celldevbio.github.io/blog/.

Mathematical Oncology

The SMB Oncology welcomes Rebecca Bekker (MD Anderson Cancer Center) as new subgroup co-chair. We thank Linh N Huyn for her dedicated engagement as co-chair for the past two years.
Social media: We like to encourage new members to check out the Social media presence of the SMB subgroup. https://mathematical-oncology.org/smb-mathonco. There you can post your articles in the Newsletter, read our blogs and even write a blog, make some art, and sign up for the weekly newsletter.

Upcoming Conferences and Programs

Biomath 2026

The next conference from the series of International Conferences on Mathematical Models and Methods in Biosciences (Biomath) takes place at the Bolyai Institute of the University of Szeged, Szeged, Hungary, from 15 to 20 June 2026. Website: www.math.u-szeged.hu/biomath2026

The series is devoted to recent research in life sciences based on applications of mathematics as well as mathematics applied to, or motivated by, biological studies. It is a meeting forum for researchers who develop and apply mathematical and computational tools to the study of phenomena in the broad fields of biology, ecology, medicine, biotechnology, bioengineering, environmental science, etc.

What Biomath 2026 offers:

Presentations by top class keynote speakers.
Opportunity to share your research.
Opportunity to publish in the journal Biomath (Scopus, DOAJ, MathSciNet, zbMATH), https://biomath.math.bas.bg/biomath/index.php/biomath
Opportunity to meet and interact with researchers in this interdisciplinary area, build links, establish collaborative networks.
School for Young Scientists for kick starting an academic career in Biomathematics.
Research stimulating environment at the Bolyai Institute of the University of Szeged.
Experiencing diverse cultures and backgrounds as well as the rich historical heritage of the location.

The Biomath conferences additionally offer a relaxed environment with lots of opportunities for discussion and meeting new colleagues.

Details on participation can be found on the conference web site: www.math.u-szeged.hu/biomath2026

Sydney Mathematical Research Institute (SMRI) International Visitor Program (IVP)

The 2026 February Round applications are now open. Researchers in the mathematical sciences from international universities who wish to do research at SMRI either individually or as part of a group of collaborators are warmly invited to apply.

This round is for visits taking place between January – December 2027 for general applicants; and September 2026 – December 2027 for Aus & NZ citizens working overseas.

Applications will close on Tuesday 17th February 2026 (11:59 pm AEST). (NB: The next application period will be open between June – August 2026).

Applications (with the information requested in the terms and conditions) must be made through the webform found on the IVP webpage.

Royal Society Publishing

Royal Society Publishing has recently published a theme issue of Interface Focus entitled Integrating Ethics into Infectious Disease Modelling: Case Studies and Perspectives from the COVID-19 Pandemic organised by Cameron Zachreson and Joel Miller and the articles can be accessed at https://bit.ly/RSFS154.

Additionally, the following theme issues from Philosophical Transactions B have been recently published:

A solid base for scaling up: the structure of numeration systems compiled and edited by Andrea Bender, Jean-Charles Pelland, Simon J Greenhill and Mary Walworth and the articles can be accessed directly at www.bit.ly/PTB1937

Origins of life: the possible and the actual compiled and edited by Ricard Solé, Chris Kempes and Susan Stepney and the articles can be accessed directly at www.bit.ly/PTB1936

"A mathematical theory of evolution": phylogenetic models dating back 100 years compiled and edited by Noah A Rosenberg, Tanja Stadler and Mike Steel and the articles can be accessed directly at https://bit.ly/PTB1919

And from Philosophical Transactions A - the following theme issue recently published:

Biological fluid dynamics: emerging directions compiled and edited by Smitha Maretvadakethope, Marco Polin, David J Smith and Laurence G Wilson and the articles can be accessed directly at www.bit.ly/TransA2304

A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org

People Section

By Ryan Murphy

Read our interview with Professor Richard Bertram, Chair of the SMB Mathematical Neuroscience subgroup, member of the SMB Board of Directors, and Professor in the Department of Mathematics at Florida State University.

Editorial

By Sara Hamis and Olivia Chu

Principles of Community

During the General Assembly meeting at the 2025 SMB Annual Meeting in Edmonton, Canada, the SMB community voted to adopt a set of Principles of Community for our society. Anyone can now access the adopted principles on the SMB website by going to the Community --> Principles of Community tab.

These guiding Principles of Community were developed by the SMB Community, Inclusion and Engagement (CIE) team (formerly the Diversity, Equity, and Inclusion team). The document reiterates the society’s goals and mission and outlines ethical professional conduct and research practices; guidelines for supporting a diversity of views, opinions, and identities; and guidelines for respectful interactions. The team used codes of conduct from several professional organizations (SIAM, AMS, MAA, Society for Freshwater Science, etc.) to inform these guiding principles. The society is interested in using these Principles to further develop a Code of Conduct for the community, which requires legal counsel and a clear framework for reporting incidents and for follow-up measures. The CIE team welcomes any suggestions and feedback from SMB community members.

- SMB Community, Inclusion and Engagement Team

Engaging with SMB

Subscribe to Forums:
- On the landing page of SMB (https://smb.org/), go to the Communications tab
- Under the Communications tab, select Member Forum
- In the top left, select the "Subscribe to forum" link
- This will prompt you to log in with your SMB username and password
- Once logged in, select the "Subscribe to forum" link.
- If you want to make a post to the forums (emailed out to other SMB members that are subscribed), click the "Create topic" button. This could be to advertise a workshop, job/Ph.D. openings, etc.
Listen to the SMB Podcast, Biology in Numbers, on Apple Podcasts or Spotify.
Follow us on social media
- X: @SMB_MathBiology
- Instagram: @smbmathbio
- Threads: @smbmathbio
- Bluesky: @smbmathbiology.bsky.social

Featured Figure

By Ananth Vedururu Srinivas

In this issue, we feature the work of Kit Gallagher and co-authors in their recent paper, Deriving Optimal Treatment Timing for Adaptive Therapy: Matching the Model to Tumor Dynamics.

We asked Dr. Gallagher to tell us a bit more about his work:

Gallagher et al. (2025) investigate how enforcing clinically realistic monitoring windows affects the treatment benefits of adaptive therapy (AT). AT aims to extend a patient’s time to progression (TTP) by maintaining a drug-sensitive subpopulation to compete with & suppress resistant cells. However, prior theoretical treatment protocols have assumed continuous tumor monitoring, which is unrealistic in standard clinical practice.

When simulating AT with discrete monitoring, the numerical simulations in Panels A and B show that shorter monitoring intervals enable a greater TTP, as they allow higher treatment thresholds that maximize competitive suppression of resistant cells. However, the heatmap in Figure 3(d) demonstrates a critical limit to this benefit: a ‘premature failure’ region (upper right) where infrequent monitoring combined with high thresholds allows the sensitive population to grow beyond the progression limit between measurements. To determine the optimal treatment protocol, Gallagher et al. (2025) derive an analytic expression for this boundary, defining the maximum safe threshold N* for a given interval (plotted in Panel C). This analytic curve matches the region of maximum TTP observed in the numerical simulations (Panel D), confirming that the standard ‘AT50’ protocol is optimal only for a specific appointment frequency.

The results characterise a quantifiable trade-off: maintaining a larger tumor burden (N*) maximizes competitive suppression of resistant cells and extends TTP, but requires more frequent clinical appointments to maintain tumor control. The authors’ analytic framework enables clinicians to balance the challenges of more frequent visits against the therapeutic benefit of extended tumor control. For details, see Gallagher et al. (2025).

In our next issue...

Get to know our new Newsletter editors
Read about research, teaching, and mentoring activities at small liberal arts colleges (SLACs) and primarily-undergraduate institutions (PUIs)

BMB Article Highlight: Miriam Schirru et al. (2025)

Fri, 12 Dec 2025 20:15:05 GMT

Generation of Virtual Populations for Quantitative Systems Pharmacology Through Advanced Sampling Methods

by Miriam Schirru, Tristan Brier, Maxime Petit, Didier Zugaj, Pierre-Olivier Tremblay, and Fahima Nekka

Quantitative systems pharmacology (QSP) models are designed to capture biological complexity and variability, and their utility increasingly relies on the generation of virtual populations (Vpop). Generating high-quality Vpop remains challenging due to nonlinear, high-dimensional, and often non-identifiable nature of QSP models. We adapted the multi-chain DREAM(ZS) MCMC algorithm to QSP and compared it against Metropolis-Hastings using the van de Pas cholesterol model. DREAM(ZS) achieved broader parameter space coverage, restored correlation structures, and generated more diverse Vpop without sacrificing model fit. It offers a flexible framework for QSP, not only for steady-state but also for future applications involving dynamic outputs.

Overview of the DREAM(ZS) algorithm applied to quantitative systems pharmacology modeling, showing its workflow, comparison with Metropolis-Hastings, and improvements in virtual population generation.

BMB Article Highlight: Soyoung Park et al. (2025)

Fri, 05 Dec 2025 13:08:14 GMT

Mathematical assessment of the roles of vaccination and Pap screening on the burden of HPV and related cancers in Korea

by Soyoung Park, Hyunah Lim, and Abba B. Gumel

Despite the availability of highly effective vaccines, Human Papillomavirus (HPV) remains a major public health challenge in Korea, causing almost all cases of cervical cancer and a significant portion of other non-cervical cancers. We developed a novel sex-structured model to assess the impact of current and proposed strategies for HPV control in Korea. Our analysis revealed that, while the current strategy of vaccinating females (at 88% coverage) combined with Pap screening will fail to eliminate HPV, strategies based on increasing the coverage of the female vaccination or adding the vaccination of boys (at 65% coverage or higher) will eliminate HPV. Our findings offer insights to guide HPV prevention policies in Korea.

Schematic illustration of model-based evaluation of HPV vaccination and cervical cancer screening strategies in Korea

BMB Article Highlight: Angela Monti et al. (2025)

Wed, 26 Nov 2025 20:41:28 GMT

Transient Instability and Patterns of Reactivity in Diffusive-Chemotaxis Soil Carbon Dynamics

by Fasma Diele, Andrew L. Krause, Deborah Lacitignola, Carmela Marangi, Angela Monti, and Edgardo Villar-Sepúlveda

Microbes in the soil play a key role in the carbon cycle by breaking down organic matter and influencing whether carbon is stored or released into the atmosphere. This study uses a simplified mathematical model to explore how microbes respond to chemical signals, a behavior known as chemotaxis, which can lead them to cluster in specific areas. These clusters may form "hotspots" of carbon activity. We show that traditional theories don't fully explain how these hotspots emerge, especially in two-dimensional models where temporary growth and nonlinear effects are important. Understanding these dynamics can improve predictions of carbon storage and emissions, helping guide climate strategies and sustainable soil management.

Microbial chemotaxis drives clustering around organic carbon, creating hotspots of activity. Stability analysis reveals regions of transient and asymptotic instability as chemotactic sensitivity increases, while simulations show spatial patterns and bifurcation curves linking heterogeneity to chemosensitivity.

BMB Article Highlight: Mariya Ptashnyk & Chandrasekhar Venkataraman (2025)

Fri, 21 Nov 2025 20:34:52 GMT

Multiscale Modelling, Analysis and Simulation of Cancer Invasion Mediated by Bound and Soluble Enzymes

by Mariya Ptashnyk and Chandrasekhar Venkataraman

We develop a framework in which cell-scale models for ECM degradation by bound and soluble matrix degrading enzymes (MDEs) can be incorporated within a macroscopic model for cancer cell invasion of the ECM. Also, we propose a methodology for computing the effective diffusivity of soluble molecules in a tissue made up of cancer cells and ECM with varying volume fractions. We analyse the coupled system of ODE-PDEs that serves as an effective model for cancer cell invasion of the ECM and present numerical simulation results of invasive processes. Interestingly, we observe the crucial role bound MDEs appear to play in determining both the speed of invasion and spatial heterogeneity in the invasive front, consistent with previous experiments.

Multiscale Modelling, Analysis and Simulation of Cancer Invasion Mediated by Bound and Soluble Enzymes

BMB Article Highlight: Rui-Wu Wang et al. (2025)

Thu, 13 Nov 2025 18:29:18 GMT

Periodic Oscillations and Transient Dynamics Caused by Saturating Density-Dependent Beneﬁts and Costs in Obligate Mutualisms

by Xue-Meng Song; Feng Zhang; Yan-Ping Liu; Ming-Rui Song; Jia-Xu Han; Rui-Wu Wang

A two-species mutualism model employs saturating functional responses to explicitly differentiate between mutualistic benefits and costs. The density-dependent nature of these benefits and costs, by differentially regulating population reproduction and mortality, provides an intrinsic mechanism that can drive periodic oscillations and transient dynamics, even in obligate mutualisms. In contrast to the conventional view, which attributes such complexity to external forces like environmental change or other species interactions, these findings reveal a potent endogenous cause. This insight offers a significant perspective for understanding ecosystem stability.

Saturating density-dependent benefits and costs can intrinsically drive periodic oscillations and transient dynamics in obligate mutualisms.

BMB Article Highlight: Yue Wang & Xueying Tian (2025)

Wed, 05 Nov 2025 19:39:43 GMT

QWENDY: Gene Regulatory Network Inference by Quadruple Covariance Matrices

by Yue Wang, Xueying Tian

In this paper, we study how to infer the regulatory relations between genes, where the input is the single-cell expression levels of genes at four time points. Due to technical limitations, each cell can be measured only once. Thus we have four probability distributions without their joint distribution, and we want to solve this dynamics. Our approach is to study how the covariance matrix evolves, and solve it analytically without any optimization. Our method, named QWENDY, ranks the first among 17 methods on three experimental data sets.

QWENDY method: solving gene regulation from covariance

BMB Article Highlight: Thomas J. Jewell et al. (2025)

Fri, 31 Oct 2025 18:34:25 GMT

Chase-and-Run and Chirality in Nonlocal Models of Pattern Formation

by Thomas J. Jewell, Andrew L. Krause, Philip K. Maini, Eamonn A. Gaffney

We study how “chase-and-run” dynamics, where one group pursues while another escapes, are influenced by chirality, a left–right bias in movement seen in animals and cells. Using nonlocal (integro-differential) advection-diffusion models, we show that angled, chiral motion can strengthen pattern formation, prevent oscillations, and generate novel behaviours like rotating pulses of chasers and runners. We also show how these dynamics can determine whether populations mix or separate. By comparing linear stability analysis with numerical simulations, we reveal when standard theory holds and when it fails. Overall, our results highlight chirality’s potential broader role in shaping ecological and developmental patterns.

Left, a schematic showing a chiral chase-and-run interaction with a chaser cell, c, pursuing a runner cell, ρ. Their movement has a consistent clockwise or anticlockwise bias parameterised by the angles α. Right, a phase diagram of the model, showing the patterning outcome at different values of the chiral running angle and the ratio of diffusivities. Coloured regions are predicted by linear stability analysis and marked points are from numerical simulations.

Biology in Numbers - Episode 3.2: Olivia Walch

Tue, 28 Oct 2025 22:00:00 GMT

…where we talk body clocks, timing your meds and, Ways and Means Subcommittees.

Dr. Olivia Walch is the CEO of Arcascope and an investigator at the University of Michigan, where she studies the mathematics of sleep and circadian rhythms through simulations and wearable devices.

She also has a penchant for boots in the winter.

Find out more about Olivia’s work at Arcascope: https://arcascope.com/

Buy her book Sleep Groove on bookshop.org

And for those of you wanting to learn more about the Geometry of Gerrymandering, check out the 2Scientists podcast episode with Dr. Thomas Weighill: https://2scientists.org/podcast/gerrymander.

Find out more about SMB on:

BMB Article Highlight: Yves Dumont (2025)

Thu, 23 Oct 2025 18:48:23 GMT

On the Improvement of the Sterile Insect Technique by Entomopathogenic Fungi: Impact of Residual Fertility and Re-mating Behaviour

by Yves Dumont

The Sterile Insect Technique (SIT) is a pest/vector control method that releases sterile males to disrupt reproduction. In Réunion, CIRAD's AttracTIS project targets the oriental fruit fly, studying how factors like residual fertility (ε), re-mating, and changes in female mating behavior affect SIT effectiveness. An analysis of our SIT structured model shows SIT works only if εR_S < 1, where R_S is the basic offspring number of sterile-mated females. Typically, the biology of double-sterile-mated females is overlooked. Combining SIT with entomopathogenic fungi, which shorten insect lifespans and reduce R_S, can allow for lower radiation doses, and thus improve sterile male fitness, or reduce the release rates.

The compartimental diagram related to the SIT structured model with re-mating and residual fertility.

BMB Article Highlight: Scott Greenhalgh et al. (2025)

Thu, 23 Oct 2025 06:50:49 GMT

Dynamics and Persistence of a Generalized Multi-strain SIS Model

by Scott Greenhalgh, Tabitha Henriquez, Michael Frutschy, and Rebecah Leonard

Non-autonomous differential equation compartmental models are powerful tools for predicting trajectories of recurrent epidemics. However, using these models can complicate solution analysis compared to their autonomous counterparts, as the criteria for understanding long-term behavior are often only computable numerically. Our work presents a simple, yet general, non-autonomous SIS model with algebraic expressions for the stability and coexistence criteria of multi-strain periodic solutions, as well as a single-strain asymptotically periodic solution in terms of elementary functions. To illustrate our model’s utility, we fit it to US syphilis data, assessing its ability to match past trends and its predictive accuracy for future outbreaks.

A non-autonomous multi-strain SIS model: persistence of periodic solutions, co-existence, and an asymptotically periodic single-strain solution in terms of elementary functions.

BMB Article Highlight: Adriana Acosta-Tovar & Fabio Lopes (2025)

Thu, 16 Oct 2025 06:06:36 GMT

Who should be controlled? The Role of Asymptomatic Individuals, Isolation and Switching in the Dominant Transmission Route in Classical and Network Epidemic Models

by Adriana Acosta-Tovar and Fabio Lopes

Understanding how infectious diseases spread is key to designing effective control strategies. We developed mathematical models to study infections with both direct (person-to-person) and indirect (environmental) transmission, using classical and EBCM-based approaches. Incorporating population heterogeneity gave a more realistic view of dynamics. We found that dominant pathways can shift over time—direct contact early on, environmental exposure later—showing the risk of relying only on early data. Our analysis highlights asymptomatic spread and the effectiveness of isolating symptomatic cases. These insights, relevant to diseases like Mpox or cholera, provide stronger tools for timely public health interventions.

Who Should be Controlled? An early dominance of direct transmission may shift toward indirect transmission in heterogeneous networks. In such cases, effective control may require a combination of isolation and environmental measures. This switching phenomenon also occurs in the homogeneous model and in Poisson networks.

BMB Article Highlight: Jeremis Morales-Morales et al. (2025)

Thu, 16 Oct 2025 05:58:30 GMT

Enhancing pedagogical practices with Artificial Neural Networks in the age of AI to engage the next generation in Biomathematics

by Jeremis Morales-Morales, Alonso Ogueda-Oliva, Carmen Caiseda, and Padmanabhan Seshaiyer

We propose leveraging both low-code and high-code programming approaches to facilitate a deeper understanding of Physics-Informed Neural Networks (PINNs) among the general student population, using the widely recognized SIR epidemiological model as a motivating example.

C-MATH with PINN Framework.

Biology in Numbers- Episode 3.1: SMB 2025

Wed, 08 Oct 2025 20:51:33 GMT

…where we talk conference things in Canada.

The annual SMB meeting is THE international gathering for mathbio nerds, and this year was no exception. 673 conference attendees traveled from 34 countries around the world to meet up in Edmonton, Canada. Join us to learn more from some of these researchers and work on social media in outbreaks, bibliometric analyses and the occasional elk sighting.

[00:41] Adam MacLean, University of Southern California, USA.
[05:08] Amy Hurford, Memorial University, Newfoundland and Labrador, Canada.
[09:45] Francisca Olajide, University of Ottawa, Canada.
[16:41] Gosia Weh, Moffitt Cancer Center, Florida, USA.
[22:16] Kira Pugh, Uppsala University, Sweden.
[25:35] Luis Sordo Vieira, University of Florida, USA.
[28:22] Mobolaji Williams, Howard University, Washington DC, USA.
[33:43] Paul Macklin, Indiana University, USA.
[41:01] Parmvir Bahia, Scientists Inc, Tampa, USA & Artha Science Media, London, UK.
[47:15] Thomas Woolley, Cardiff University in Wales, UK.

Find out more about SMB on:

BMB Article Highlight: Geoffrey R. Hosack et al. (2025)

Thu, 02 Oct 2025 07:41:45 GMT

Stability of difference equations with interspecific density dependence, competition, and maturation delays

by Geoffrey R. Hosack, Maud El-Hachem and Nicholas J. Beeton

The stability properties of delayed discrete-time model of interspecific competition are examined using directed graphs (figure). For a competitive multi-species model that extends the Beverton-Holt model, return towards the coexistence equilibrium after a local perturbation is guaranteed if intraspecific competition is stronger than interspecific competition. The rate of return depends on the species composition. This property is used to predict an optimised configuration of interspecific competition and rate of return for a system of morphologically indistinguishable species: Although direct observation of the species abundances in the field is not possible, available genotyping methods provide information on species composition.

Directed graph for three species that connects the nodes of age classes zero (immature recruits) to mature adult stage individuals of age class delta with arcs: survival transitions are shown by red arrows, density dependent recruitment by black arrows, and interspecific interactions by blue arrows. These arcs form cycles that in turn provide sufficient conditions for the stable coexistence of species.

BMB Article Highlight: Hiroshi Toki et al. (2025)

Thu, 25 Sep 2025 16:46:40 GMT

Theoretical Study of Retinoblastioma in the Hereditary and Non-hereditary Processes including the Cancer Growth

by Hiroshi Toki, Yoshiharu Yonekura, Yuichi Tsunoyama, and Masako Bando

Knudson’s two-hit hypothesis distinguished hereditary from sporadic cancers, but real-world incidence
often deviates from its predictions. Our 2P2H (two-period, two-hit) model refines this by incorporating
period-specific mutation rates, particularly after the proliferative phase of retinal cells. We propose that
mutation processes differ fundamentally between proliferative and post-developmental stages. Using
differential equations, we model the temporal evolution of mutation accumulation and cancer onset, while
also accounting for diagnostic time lag—a factor absent in Knudson’s theory. The 2P2H model
accurately reproduces observed incidence curves, resolving prior inconsistencies. We believe it provides
a more precise, biologically grounded framework for understanding cancer initiation.

The 2P2H Model.

BMB Article Highlight: Solveig A. van der Vegt et al. (2025)

Thu, 18 Sep 2025 14:54:28 GMT

Optimal Control of Immune Checkpoint Inhibitor Therapy in a Heart-Tumour Model

by Solveig A. van der Vegt, Ruth E. Baker, and Sarah L. Waters

In modelling the impact of cancer therapy, side effects are almost never explicitly considered, despite the severe risk they can pose to patients. Notably, immune checkpoint inhibitors (ICIs), a commonly used class of drugs, can cause autoimmune myocarditis. This paper presents a framework for optimising the timing of doses of ICIs, where both the effects on the tumour and on the heart are explicitly considered. It demonstrates that it is feasible, in regimes where standard-of-care schedules lead to autoimmune myocarditis, to identify dosing schedules that prevent cardiac side effects while inhibiting tumour growth. This framework represents a significant advancement towards the modelling of safe and effective cancer therapies.

A framework combining optimal control theory and a heart-tumour model which explicitly considers both the effects on the tumour and on the heart, can identify dosing schedules that prevent cardiac side effects while inhibiting tumour growth.

BMB Article Highlight: John M. Myers &Hadi Madjid (2025)

Wed, 10 Sep 2025 16:58:06 GMT

Computations in living organisms modeled by marked graphs

by John M. Myers and Hadi Madjid

Cognition and other biological processes, including human thinking, are subject to unpredictable changes. Thus, computation is a part, but by no means the whole, of cognition. The paper is philosophical in that we propose a novel way in which humans and other living organisms are more than computers. We propose that biological organisms perform computations that are continuously being re-wired by something external. Ignoring for the moment what this external something might be, we provide the mathematical tools to simulate this re-wiring. In this way we provide thought tools for asking new questions-and sometimes answering them-about the intertwined role of logical operations and surprises in biology.

Surprises reset clocks.

Summer 2025 Newsletter

Mon, 08 Sep 2025 23:59:26 GMT

Olivia Chu (Bryn Mawr College), Ryan Murphy (University of South Australia), Ananth Srinivas (LSU Health New Orleans), and Sara Hamis (Uppsala University). Welcome to Ryan, Ananth, and Sara, the newest members of our newsletter team!

Reminders from SMB's new President, Reinhard Laubenbacher.
News - Updates from:
People - Interview with Dr. Binod Pant, Network Science Institute (NetSi) at Northeastern University.
Editorial - A note from the Bulletin of Mathematical Biology.
Featured Figure - Daniel Netherwood, The University of Adelaide.

To read the subsections of this issue, click the links at the above items.

Contributing content

We welcome submissions to expand the content of the newsletter. The next issue will be released in the Fall, so if you would like to contribute, please send an email to the editors by the start of November 2025 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the Member Forum rather than to the newsletter.

Finally, be sure to follow us on social media:

We hope you enjoy this issue of the newsletter!

Olivia, Ryan, Ananth, and Sara
Editors, SMB Newsletter

A Message from Reinhard Laubenbacher

We warmly welcome SMB's new President, Professor Reinhard Laubenbacher, who is the Director of the Laboratory for Systems Medicine at the University of Florida. We also thank outgoing President Jane Heffernan for her dedicated service to the Society.

Professor Laubenbacher wants to hear from you about your experiences with SMB, what issues you want SMB to focus on, initiatives you would like to see, challenges you are dealing with, and successes you have achieved. You can write to him at reinhard.laubenbacher@medicine.ufl.edu.

In late August, Professor Laubenbacher shared his first President's Letter with the community. Below, we highlight some exciting recent developments at the SMB in case you missed them.

Early-career researchers.

At the 2025 annual meeting in Edmonton, CN, the membership at the General Meeting approved the expansion of the SMB Board of Directors by two seats, both reserved for early career researchers (within 5 years of Ph.D. or equivalent degree). This is the first step of an initiative to better meet the needs of this community within SMB. For the upcoming Board elections, please nominate candidates for these seats (including self-nomination).

New SMB Sections Program.

Also at the Edmonton meeting, the Board voted to establish a Sections program, modeled after a similar program SIAM has established. Regional and national sections will bring SMB closer to its members, provide more opportunities for engagement, offer more scientific meetings, and expand the global reach of SMB. More details to come.

Global Outreach.

SMB has signed a Memorandum of Understanding with SoLaBiMa, the Latin American Society for Mathematical Biology. The two societies will work together to support mathematical biology in Latin America, including joint sponsorship of the biannual conference SoLaBiMa has been organizing. The 2026 conference will take place in Paraguay. Similar efforts in other parts of the world are in the works or in planning stages, including in Africa.

News Section

By Ryan Murphy

In this issue of the News section, we highlight the updates from the SMB Subgroups, Royal Society Publishing, and an upcoming workshop. Read on below.

SMB Subgroups Updates

Cell & Developmental Biology

Link to blog: https://smb-celldevbio.github.io/
CDEV Subgroup membership has increased by about 2% since 2024.
During SMB 2025, we organized a two-part subgroup minisymposium “From data to mechanisms: advancement in modeling in cell and developmental biology” with 8 speakers.
We awarded 4 travel grants to early career CDEV members who traveled to attend SMB 2025 and donated $250 to the SMB 2025 Poster winners. The travel grants were awarded to Gulsemay Yigit, Rebecca Crossley, Maryam Alka and Ruby Nixson. .https://smb-celldevbio.github.io/2025-06-22-Special-SMB-Travel-Grant/
The SMB CDEV poster session winners were Karen Enumah (Clarkson University) and Julio Belmonte (NC State University).
In Fall 2025, the SMB CDEV Subgroup will host job search series, where we will have mock interviews and details on the hiring process for both academic and industry positions. More details will be sent via list serv and posted on the CDEV Blog.
In Spring 2026, the SMB CDEV Subgroup will have a virtual research session. Attendees will have the opportunity to talk about their research in 3-minute lightning rounds, as well as ask questions and network with other attendees.

Immunobiology & Infection

The Immunobiology and Infection Subgroup is collecting nominations for both the Subgroup Chair and Secretary positions for terms beginning at the 2026 SMB Annual Meeting. Elections will be held in early 2026. Please consider nominating yourself or a colleague for these positions (see descriptions of each below). We are excited to see the subgroup’s growth and momentum keep going in the coming years!

The Subgroup Chair organizes and conducts group meetings, advises the Society for Mathematical Biology of the group’s activities and needs, and carries on any other activities which the Chairperson deems to be beneficial to IMMU and to the Society. The Secretary keeps adequate membership records of membership and works with the Chairperson on organizational and financial matters relating to IMMU.

Mathematical Neuroscience

The Mathematical Neuroscience subgroup hosted a successful virtual mini-conference https://sites.google.com/brandeis.edu/smb-mathneuro-2025 on July 12-13, 2025. This event featured 10 invited speakers, 12 contributed talks, and attracted over 230 registered participants across multiple time zones. During the annual SMB meeting 2025, our subgroup held a social gathering - a great opportunity to connect in person while enjoying the talks and posters. Additionally, the subgroup is now gathering interests in officer positions for the 2025-2027 term and expect to announce the new team soon.

Mathematical Oncology

1. We want to make the community aware of the upcoming Mathematical Oncology Conference at the end of October (evening of the 28th-31st) on the St. Pete beach in Florida. The goal of this recurring meeting is to provide an international venue for collaboration, integration, training and synergy for mathematical oncology research. A major focus of this conference will be Evolutionary Therapy but not exclusively so and there will be an emphasis on junior investigators. More info is available here: MathOnco25, including the opportunity to apply for travel awards. There is also the chance for conference participants to stay the weekend and attend the 13th IMO Workshop.

2. There is a special issue of Mathematical Biosciences devoted to the memory of Professor Siv Sivaloganathan. Dr. Sivaloganathan (University of Waterloo) made many important contributions to mathematical medicine, including modeling of hydrocephalus and tumor growth, treatment responses, and the evolutionary dynamics of cancer cells. You can read more about this special issue, entitled "Perspectives on Mathematical Oncology" here: Mathematical Biosciences | ScienceDirect.com by Elsevier - Mathematical Biosciences | ScienceDirect.com by Elsevier. All participants of the Thematic Program on Mathematical Oncology from the Fields Institute, July-Dec 2024 in Toronto, CAN are encouraged to submit to this special issue.

Summer 2025 Newsletter (continued)

Mon, 08 Sep 2025 23:54:45 GMT

Royal Society Publishing

New issues of interest from Royal Society Publishing Philosophical Transactions A:

Generative modelling meets Bayesian inference: a new paradigm for inverse problems compiled and edited by Alain Oliviero-Durmus, Yazid Janati, Eric Moulines, Marcelo Pereyra and Sebastian Reich and the articles can be accessed directly at www.bit.ly/TransA2299

Partial differential equations in data science organised and edited by Andrea L Bertozzi, Nadejda Drenska, Jonas Latz and Matthew Thorpe and the articles can be accessed directly here.

A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org.

Upcoming Workshop

Dear colleagues,

We are happy to announce the third edition of the workshop on "Modelling Diffusive Systems: Theory and Applications" (MoDiS), which will take place at the Erwin Schrödinger Institute (ESI) in Vienna during the week 26-30 January 2026.

The list of speakers and the preliminary schedule are both available on the workshop website. There is a limited number of spots for additional participants - priority will be given to early-career researchers who are also encouraged to present a poster. In order to apply, please fill out the registration form available at this link by September 15.

We look forward to seeing you in Vienna!

Best,

Valeria Giunta, Annalisa Iuorio, Angelika Manhart, and Cinzia Soresina

People Section

By Ananth Srinivas

Dr. Binod Pant speaks with our new Newsletter Editor, Ananth Vedururu Srinivas. Binod is a postdoc at the Network Science Institute (NetSi) at Northeastern University in Boston, Massachusetts and is a new Co-Chair of the Mathematical Epidemiology Subgroup.

Read our interview with Dr. Pant here.

Editorial

By Olivia Chu

The Society for Mathematical Biology welcomes submissions to the Bulletin of Mathematical Biology (BMB), the flagship journal of the Society. The SMB is continuing its longstanding relationship with Springer-Nature as the publisher of BMB for another 7 years. Here, we share and encourage you to read an Editorial by the current Editor-in-Chief of BMB, Matthew Simpson, President of the SMB and former Editor-in-Chief of BMB Reinhard Laubenbacher, and Chair of the SMB Publications Committee Jennifer Flegg on publishing in BMB.

Featured Figure

By Sara Hamis

In this issue, we feature the work of Daniel Netherwood and co-authors in their recent paper, Accidental and Regulated Cell Death in Yeast Colony Biofilms.

We asked Dr. Netherwood to tell us a bit more about his work:

Netherwood et al. (2025) investigate how the mechanisms of accidental (e.g., necrotic) and regulated (e.g., apoptotic) cell death affect the expansion speed, morphology, and cell distribution of yeast colony biofilms. Motivated by their own experiments (see fig xx) using Saccharomyces cerevisiae (the baker’s yeast) colony biofilms grown on an agar substrate, Netherwood et al. (2025) propose a continuum model for yeast biofilm expansion involving a four-species system of nonlinear reaction–diffusion equations for the living yeast-cell density, the nutrient concentration, a species of cells that have died via accidental cell death (ACD) and a species of cells that have died via regulated cell death (RCD). Spatially one dimensional numerical solutions of this system are shown in figure (xx), where the predicted profiles for each of the four species are plotted as a function of the spatial coordinate $x$ (measured from the biofilm centre) in addition to the wave speed, each as the dimensionless rate of nutrient recovery induced by the RCD mechanism (\Gamma, a control parameter) is varied. For a parameter regime in which ACD is assumed to occur faster than RCD, qualitative agreement with the experiments is reached whereby at late time RCD cells are found to adopt a pulse-like profile following the film front, whilst the ACD cells are found to decay linearly from the biofilm centre towards the front. The wave speed is found to depend nonlinearly on the rate of nutrient recovery and agrees with the hypothesis that RCD can offer a survival advantage to the colony by increasing wave speed and hence enhancing the film's ability to invade and colonise the substrate on which it is growing. For details see Netherwood et al. (2025).

BMB Article Highlight: Uvencio José Giménez-Mujica et al. (2025)

Wed, 03 Sep 2025 17:43:20 GMT

Final size index-driven strategies for cost-effective epidemic management in metapopulation

by Uvencio José Giménez-Mujica; Jorge Velázquez-Castro; Andrés Anzo-Hernández, and Ignacio Barradas

Designing epidemic control strategies in metapopulations is essential for public health policies. In this article, we propose an efficient resource allocation methodology that considers the epidemic response and the cost of implementing a control strategy in given areas. Using a metapopulation SEIR model, we derive the final epidemic size in each area and propose an index to guide the control strategy. We compare the index with intuitive strategies: allocating all resources to the most affected area and distributing them equitably. We show that an allocation proportional to the index optimizes distribution, avoiding resource concentration in a few areas, keeping local peaks low, and ensuring a balanced epidemic impact across the network.

Right side. Epidemic peak reduction using the proposed index. Left side: Comparison of different control strategies using a network constructed with the ER algorithm.

BMB Article Highlight: Gesina Menz & Stefan Engblom (2025)

Thu, 21 Aug 2025 05:29:43 GMT

Modelling Population-Level Hes1 Dynamics: Insights from a Multi-framework Approach

by Gesina Menz and Stefan Engblom

We investigate the behaviour of the Hes1-Delta-Notch signalling pathway governing cell differentiation during neuronal development using both an ordinary differential equation (ODE) model and a related reaction-diffusion master equation (RDME) framework. The ODE model captures transient oscillatory behaviour followed by stable patterning reflecting cell differentiation into neurons and glial cells and is reduced for analytical tractability. The RDME approach, however, allows us to assess the impact of intrinsic noise on pattern formation. Together, the models show that the characteristic dynamics are robust under stochastic fluctuations and that the deterministic stability analysis reflects behaviour in the stochastic setting.

Modelling the Hes1-Notch GRN using both ODE and RDME models allows us to capture behaviour in the deterministic and stochastic settings.

BMB Article Highlight: Guyue Liu et al. (2025)

Wed, 13 Aug 2025 06:06:29 GMT

Modeling the effects of a Shock-and-Kill Treatment for HIV: Latency-Reversing Agents and Natural Killer Cells

by Guyue Liu, Suli Liu, Chiyu Zhang, Xu Chen, Wenxuan Li, and Huilai Li

Despite ART's success in suppressing HIV, viral reservoirs persist as barriers to cure. This study leverages a mechanistically grounded mathematical model, calibrated with HIV-1-infected humanized mice data via Bayesian MCMC, to decode how tripartite therapy (ART + LRAs + NK cells) eradicates reservoirs.
Key findings:

(1) NK cells are pivotal modulators - their infusion frequency and dosage critically determine cure likelihood.

(2) The tripartite therapy offers superior viral suppression and accelerated therapeutic effects, with a specific parameter region for achieving a cure of HIV.

Graphical Abstract.

BMB Article Highlight: Oluwagbemisola Oladepo & Angela Peace (2025)

Thu, 07 Aug 2025 15:09:58 GMT

Nutrient-Driven Adaptive Evolution of Foraging Traits Impacts Producer-Grazer Dynamics

by Oluwagbemisola Oladepo, and Angela Peace

Grazers like Daphnia adjust feeding to cope with changes in food quality and availability, while producers like algae vary in abundance and nutrient content. This study uses models to compare fixed and adaptive foraging strategies in grazers. Results show that adaptive foraging can support survival in nutrient-poor environments, acting as evolutionary rescue. However, rapid adaptation may lead to population fluctuations and increase extinction risk. These findings highlight when adaptive foraging aids grazer persistence and when it may destabilize ecosystems, informing our understanding of ecological resilience.

Nutrient-Driven Adaptive Evolution of Foraging Traits Impacts Producer-Grazer Dynamics: A Graphical Abstract.

BMB Article Highlight: Julia Bruner et al. (2025)

Wed, 30 Jul 2025 15:42:31 GMT

Understanding Immune Dynamics in Liver Transplant Through Mathematical Modeling

by Julia Bruner, Kyle Adams, Skylar Grey, Mahya Aghaee, Sergio Duarte, Ali Zarrinpar, and Helen Moore

Liver transplantation is a life-saving procedure for the treatment of end-stage liver disease. However, transplant recipients must take immunosuppressive medications for the rest of their lives, in order to prevent their immune system from attacking and causing damage to the donor liver (known as “rejection”). Although immunosuppressive therapies are necessary to prevent rejection, extended or excessive immunosuppression can lead to life-threatening infections or cancer. We built and analyzed a mechanistic mathematical model to study the immune dynamics involved in the balance between immunosuppression and rejection. Our model identified dynamics between the following quantities as most critical to this immune balance: a type of immune cell called cytotoxic T cells; the inflammation-modulating protein interleukin-2 and the transplanted liver itself.

Graphical abstract of the study.

BMB Article Highlight: David N. Levine & Ari I. Rapalino (2025)

Wed, 16 Jul 2025 13:38:56 GMT

The pathogenesis of papilledema: review of the literature and a new hypothesis

by David N. Levine and Ari I. Rapalino

Papilledema, or swelling of the head of the optic nerve, occurs when intracranial pressure exceeds intraocular pressure to an abnormal degree. We conducted a biomechanical analysis of the effect of such excess pressure on the optic nerve. The stresses created in the nerve are: 1) a gradient of tissue pressure and 2) an axially oriented shear stress. Both are sharply localized to the region where the optic nerve exits the eye, and the excessive external pressure on the nerve begins. The gradient of tissue pressure liquifies the axoplasmic gel inside some of the axons – particularly those of large diameter located peripherally in the nerve cross-section - and displaces it towards the cell body, causing swelling of the optic nerve head.

High intracranial pressure displaces axoplasm from the extraocular portion of the optic nerve into the intraocular portion, causing swelling of the head of the optic nerve.

BMB Article Highlight: Pierre Monmarché et al. (2025)

Thu, 10 Jul 2025 19:44:07 GMT

Impacts of Tempo and Mode of Environmental Fluctuations on Population Growth: Slow- and Fast-Limit Approximations of Lyapunov Exponents for Periodic and Random Environments

by Pierre Monmarché, Sebastian J. Schreiber and Édouard Strickler

This work derives analytical approximations for how environmental fluctuation frequency affects population growth in structured populations experiencing periodic or random switching between environmental states. Key findings: (1) In slow-switching limits, periodic and random fluctuations have equivalent effects on growth rates, but differ significantly in fast-switching limits. (2) Applications to metapopulation models show that slower environmental switching promotes persistence, with random environments allowing higher switching frequencies for persistence than periodic ones. The results demonstrate that both tempo (frequency) and mode of environmental fluctuations critically influence population dynamics.

Population growth rates in a fluctuating two-patch environment. Both tempo (slow vs. fast) and mode (random vs. periodic) can determine persistence.

Biology in Numbers- Episode 2.10: Jay Newby

Wed, 02 Jul 2025 17:11:11 GMT

… where we talk: Random openings in neurons, Gumbatine, and conferences in Canada.

Jay Newby graduated from the University of Utah Math Biology program in 2010. He was supervised by Paul Bressloff. His expertise includes applied stochastic processes, mathematical modeling, and machine learning tools for bio-image analysis systems.

Learn more about Jay’s work on his webpage: https://sites.ualberta.ca/~jnewby/
Find the weather app we talked about here: earth.nullschool.net
And you can find out about SMB’s annual meeting here: https://2025.smb.org/.

Find out more about SMB on:

BMB Article Highlight: Farshad Shirani & Judith R Miller (2025)

Wed, 25 Jun 2025 06:47:45 GMT

Matching Habitat Choice and the Evolution of a Species' Range

by Farshad Shirani and Judith R Miller

It is reasonable to think that when individuals of a species detect habitat favorable for their characteristics, they move towards it—a phenomenon called matching habitat choice (MHC). However, this behavior is relatively rare in nature, and a major goal of the present research is to understand why this is so. By developing a model of a species’ range evolution using PDEs and numerically solving the equations, we found that MHC is likely to be prevalent only in environments whose conditions change dramatically over a short distance relative to the movement ability of the organism. Further, when MHC does occur, it increases the spread rate of an invasive species and enhances the species’ chance of survival in rapidly changing environments.

Matching Habitat Choice and the Evolution of a Species' Range: A Graphical Abstract.

BMB Article Highlight: David Murrugarra et al. (2025)

Thu, 19 Jun 2025 04:30:07 GMT

Modular control of Boolean network models

by David Murrugarra, Alan Veliz-Cuba, Elena Dimitrova, Claus Kadelka, Matthew Wheeler, and Reinhard Laubenbacheri

Modeling Innate Immunity Causing Chronic Inflammation and Tissue Damage

Control problems in biological systems involve identifying effective interventions to drive the system toward a desired outcome. These strategies are typically guided by mathematical models, where the objective is to find suitable control inputs such as gene knockouts that alter system behavior in a predictable way. In this paper, we introduce a modular approach for controlling Boolean networks, which represent biological regulatory systems using binary logic. Our method decomposes a complex network into smaller, more manageable modules, allowing for the analysis and control of each subnetwork independently. By leveraging the modular structure and the canalizing properties of regulatory functions we develop a scalable framework for control.

Graphical abstract summarizing the study.

Spring 2025 Newsletter

Mon, 09 Jun 2025 02:44:30 GMT

Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Bryn Mawr College).

News - updates from:
People - Interview with Professor Dan Coombs, University of British Columbia (UBC).
Featured Figure - Kosei Matsuo, Kyushu University.

Contributing content

We welcome submissions to expand the content of the newsletter. The next issue will be released in August, so if you would like to contribute, please send an email to the editors by the start of August 2025 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the Member Forum rather than to the newsletter.

We hope you enjoy this issue of the newsletter!

Sara, Burcu, Thomas, and Olivia
Editors, SMB Newsletter

News Section

By Sara Loo

In this issue of the News section, we highlight upcoming conferences and provide updates from the SMB Subgroups and Royal Society Publishing. Read on below.

Upcoming Conferences

SMB Annual Meeting

The SMB Annual Meeting will be held from July 13-18th, 2025 at the Edmonton Convention Center. Registration is now open! For more information, visit the conference webpage.

SMBE Regional Symposium on Evolutionary Genomics in Agriculture, Environment, Biodiversity conservation and Health for Africa, 2025

The University of Eldoret, Kenya, under the auspices and support of the Society for Molecular Biology and Evolution (SMBE) will host the SMBE Regional Symposium on Evolutionary Genomics in Agriculture, Environment, Biodiversity conservation and Health 2025, in Eldoret. The main theme of the symposium is: The role of evolutionary genomics in addressing challenges in agriculture and environment in Africa.

Key Dates

Dates of the Symposium: 8th to 11th September, 2025,
Deadline for submitting Abstracts: 7th July, 2025,
Conference registration: 15th August, 2025

https://uoeld.ac.ke/research-and-extension/smbe-regional-symposium-evolutionary-genomics-agriculture-environment

Continuum Mechanics in Biology workshop

A workshop on continuum mechanics in biology will be held at the University of Birmingham, UK, 1-3 July. Event website: https://sites.google.com/view/continuum-mechanics-in-biology/.

The proceedings will feature plenary lectures, contributed talks and posters, and interactive sandpits fostering interdisciplinary collaborations.

All researchers interested in biological applications of continuum mechanics are welcome to attend; PhD students and early career researchers are particularly encouraged to do so. Contributions of short talks and posters are keenly sought.

The link to register (by 8 June) and information about financial support available to students and carers, can be found on the event website.

SMB Subgroups Updates

Mathematical Epidemiology (MEPI)

The Mathematical Epidemiology subgroup, along with the Education subgroup, hosted a virtual mini-symposium May 20-21. We had 3 plenary speakers, 27 contributed talks, and over 130 participants registered.

Additionally, the Mathematical Epidemiology subgroup is now accepting nominations for the position of Co-Chair for the 2025-2026 year. The Co-Chair election will occur prior to the 2025 SMB Annual Meeting. The elected Co-Chair will work with Prashant Kumar Srivastava between July 2025 and June 2026 and will serve as Chair July 2026-June 2027, then as Past Chair from July 2027 through June 2028. The main responsibilities of the Co-Chair are (i) working closely with the chair on organizational and financial matters related to the subgroup, and (ii) facilitating activities of the subgroup. Serving as Co-Chair is an excellent opportunity to get involved with SMB organization and leadership!

Please submit any Co-Chair nominations to Meredith Greer (mgreer@bates.edu) before Thursday, June 5, 2025. Self-nominations are encouraged, and all nominations should include the name, position, and affiliation of the nominee along with a 1-2 paragraph biography of the nominee.

Immunobiology and Infection

The Immunobiology and Infection subgroup is looking forward to this year’s annual meeting! Allof IMMU’s activities can be found at this link. We have exciting talks (throughout) and posters (Monday night) ranging from within-host interactions to population-level transmission. Subjects of focus include Bayesian inference, and agent-based and differential equation models to understand immune responses to vaccines and infections, including cytokine regulation, antibody durability, and T cell repertoire dynamics. Work from our group will report on vaccine optimization, novel therapeutics (immunotherapies), viral rebound, latent infections, and treatment failures. One important and unifying goal of IMMU is to link experimental data to predictive models, often across biological scales, and this will be highlighted throughout IMMU presentations at SMB 2025. Keep a look out for announcements of organized activities (Wednesday afternoon) and a subgroup dinner. Looking forward to seeing members of IMMU and other subgroups in Edmonton this summer!

Mathematical Oncology

MathOnco will conduct its business meeting at the SMB 2025 Annual Meeting from 6-6:45pm on Tuesday July 15th. Following the business meeting, starting at 7pm, the MathOnco subgroup will host a social event for all members. Details will be sent around shortly!

Pharmacometrics

Jesse Kreger (University of Southern California) has joined Marissa Renardy as co-chair!
We have started a LinkedIn Group (https://www.linkedin.com/groups/13188488/) and encourage anyone interested to join.
We will be planning a networking social on the evening of Sunday, July 13 at the annual meeting. We encourage anyone interested to RSVP here so we can get an estimate of the head count: https://forms.gle/vysEeeVb9McZAube7

Royal Society Publishing

Philosophical Transactions of the Royal Society A has recently published a new special double issue - Uncertainty quantification for healthcare and biological systems (Parts I & II), compiled and edited by Louise M Kimpton, L Mihaela Paun, Mitchel J Colebank and Victoria Volodina and the articles can be accessed directly at https://bit.ly/PTA2292 and Part II here.

A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org.

People Section

By Thomas Woolley

In this newsletter’s People section, we highlight Professor Dan Coombs. He is a mathematical biologist at the University of British Columbia (UBC), where he serves as Head of the Department of Mathematics. His research applies mathematical and computational modelling to problems in immunology, virology, and public health, with work spanning from cellular receptor dynamics to within-host viral infections and population-level epidemic models. He has made significant contributions to the understanding of HIV, cytomegalovirus, and COVID-19, and has collaborated extensively with public health agencies.

Read our interview with Professor Coombs here.

Featured Figure

By Burcu Gürbüz

In this issue, we feature the work of Kosei Matsuo and Yoh Iwasa, Kyushu University:

In their 2025 study published in the Bulletin of Mathematical Biology, Matsuo and Iwasa present a mathematical model that explores the dynamics between innate immunity, chronic inflammation, and tissue damage. The model uses a system of differential equations to represent the interactions among four key variables:

1. Pathogen Abundance (z): Represents the concentration of pathogens in the body.
2. Immune Response (w): Denotes the activity level of innate immune cells responding to the pathogen.
3. Inflammation (y): Quantifies the degree of inflammation triggered by the immune response.
4. Tissue Damage (x): Measures the extent of damage inflicted on host tissues due to prolonged inflammation.

The authors propose a simplified dynamical model (Figure (1a)-(1d) below) to capture the essence of innate immune responses.

The study shows that the system can exhibit different behaviors depending on the parameter values: pathogen eradication which indicates the immune system successfully eliminates the pathogen, but inflammation may persist, leading to chronic inflammation; pathogen persistence, i.e. the pathogen remains in the body at a stable level, with ongoing immune response and tissue damage; perpetual oscillation, the system enters a state of continuous fluctuation, with oscillating levels of pathogen abundance, immune response, inflammation, and tissue damage. A key finding is that innate immunity can sometimes eradicate pathogens but leave behind chronic inflammation that can cause ongoing tissue damage. In addition, the model identifies conditions under which the system undergoes transcritical and Hopf bifurcations, leading to qualitative changes in system behavior. The study also examines the role of non-inflammatory activation of the immune response. The authors find that when innate immunity is activated independently of inflammation, pathogens are more efficiently eradicated and the likelihood of oscillatory dynamics is reduced. This study is original in its focus on modeling the interplay between innate immunity and chronic inflammation, areas traditionally less emphasized in mathematical immunology, which often focuses on adaptive immunity. The results provide valuable insights into how innate immune responses can inadvertently contribute to chronic inflammation and tissue damage, highlighting the delicate balance required in immune regulation.

Matsuo and Iwasa’s study provides a detailed understanding of how innate immune responses can inadvertently lead to chronic inflammation and tissue damage. Their mathematical model serves as a fundamental tool for further research aimed at understanding the complexities of immune dynamics and their implications for health and disease.

Fig. 1 Scheme of the model. Four variables are depicted: pathogen abundance z; immune responses w; inflammation y; and tissue damage x. Arrows indicate interactions between them. Fig. 1 illustrates the interaction between the variables.

Biology in Numbers- Episode 2.9: Marissa Renardy

Wed, 04 Jun 2025 17:35:59 GMT

… where we talk: Big pharma, In silico trials, and Sciencing for fun.

Marissa earned a PhD in Mathematics from The Ohio State University in 2018. She was then a postdoctoral research fellow at University of Michigan until 2021, when she joined Applied BioMath as a full time QSP modeler, then GSK in July 2024.

She does applied work with her mathematician parents’ full approval.

Follow Marissa’s progress on her LinkedIn page: linkedin.com/in/marissa-renardy.

Find out more about SMB on:

BMB Article Highlight: Murshed Ahmed Ovi et al. (2025)

Wed, 28 May 2025 07:31:32 GMT

Estimating Hidden Cholera Burden and Intervention Effectiveness

by Murshed Ahmed Ovi, Andrei Afilipoaei, and Hao Wang

Cholera remains a significant health issue in many developing nations. Understanding the role of asymptomatic and under-reported symptomatic cases is vital in controlling outbreaks. Our model, incorporating indirect transmission, shows these cases greatly influence spread through bacterial shedding. Key challenges include Vibrio cholerae ingestion and bacterial shedding from reported cases. Model fitting in countries like Haiti, Kenya, Malawi, and Zimbabwe estimates over 88.5% of cases are inapparent, with up to 11 weeks before detection. In high-compliance settings, sanitation and handwashing are most effective; in low-compliance areas, vaccination and safe fecal disposal are preferable for reducing cholera risk.

Estimating Hidden Cholera Burden and Intervention Effectiveness.

BMB Article Highlight: Isabelle Beach & Hana M. Dobrovolny (2025)

Wed, 21 May 2025 06:17:52 GMT

The effect of antibodies in the presence of syncytia during viral infections

by Isabelle Beach and Hana M. Dobrovolny

Many viruses can spread by fusing cells into multi-nucleated cells called syncytia. This model examines how the effectiveness of antibodies is affected by the presence of syncytia, finding that spreading through syncytia formation protects the virus from elimination by antibodies.

A mathematical model of syncytia-forming virus with an antibody response.

Biology in Numbers- Episode 2.8: Daniel Cooney

Mon, 05 May 2025 23:09:21 GMT

… where we talk: Hawks and Doves, social media and the PhD comics.

Dan Cooney is a mathematical biologist interested in modeling evolutionary dynamics across scales and exploring collective behavior in complex biological and social systems.

He also enjoys reading, traveling, and "applied game theory" to baseball and chess.

Find out more about Dan’s work on his website:https://publish.illinois.edu/danielbcooney,

or follow him on Bluesky:@danielcooney1.bsky.social

Find out more about SMB on:

BMB Article Highlight: Haoran Hu et al. (2025)

Wed, 09 Apr 2025 07:51:55 GMT

A Framework for Parameter Estimation and Uncertainty Quantification in Systems Biology Using Quantile Regression and Physics-Informed Neural Networks

by Haoran Hu, Qianru Cheng, Shuli Guo, Huifang Wen, Jing Zhang, Yongqi Song, Kaiqun Wang, Di Huang, Hui Zhang, Chaofeng Zhang, and Yanhun Shan

This study introduced a novel framework integrating quantile regression with Physics-Informed Neural Networks to enhance parameter estimation and uncertainty quantification in systems biology models. The approach demonstrated superior accuracy in parameter estimation, stronger correlation between uncertainty and noise levels, and moderate computational costs. By efficiently addressing data limitations and noise, this framework offers a powerful tool for advancing predictive biological modeling, with potential applications in drug development, disease modeling, and understanding complex biological interactions. Its scalability and reliability position is as a promising solution for real-world systems biology challenges.

The illustration of the PINN-based quantile regresion approach.

Biology in Numbers- Episode 2.7: Mohit Kumar Jolly

Wed, 02 Apr 2025 23:18:08 GMT

… where we talk changing cancer cells, awards and the Indian Institutes of Technology.

Mohit leads an interdisciplinary research team working on elucidating the dynamics of metastasis and drug resistance, through developing multi-scale mathematical models in close collaboration with experimental and clinical colleagues.

He and his group do this work powered by many cups of chai.

Find out more about Mohit’s group and their work on the following website: https://be.iisc.ac.in/~mkjolly/.

Find out more about SMB on:

BMB Article Highlight: Arianna Ceccarelli et al. (2025)

Thu, 27 Mar 2025 08:27:55 GMT

Approximate solutions of a general stochastic velocity-jump model subject to discrete-time noisy observations

by Arianna Ceccarelli, Alexander P. Browning, and Ruth E. Baker

We analyse velocity-jump models for single-agent motion in one spatial dimension, in which the agent transitions between n states, each with a set velocity and fixed switching rates to other states. Since the agent’s true state cannot be observed, computing the exact distributions of discrete-time noisy data is generally intractable. Therefore, we derive approximations for the observed data distributions, both for a single measurement and considering the correlation between locations of a tracked agent, and validate them through simulations of four model structures. These approximations enable fast predictions, guide experimental design, and can be used as likelihoods for inference and model selection.

Solutions of an example three-state model. The three-state model (panel B) comprises a forward-movement state, a backward-movement state and a stationary state. A short data track is shown in panel A. A location increment y is defined. as the difference between subsequently measured locations. Panel C compares the empirical distribution, generated with in-silico data, to one of the approximations obtained in the manuscript for single location increments. Panel D compares the empirical distribution for two subsequent location increments to the joint approximation obtained in the manuscript, and to the marginal approximation which does not take into account the correlation between subsequent location increments.

BMB Article Highlight: Kosei Matsuo & Yoh Iwasa (2025)

Thu, 20 Mar 2025 20:58:03 GMT

Modeling Innate Immunity Causing Chronic Inflammation and Tissue Damage

by Kosei Matsuo and Yoh Iwasa

We examine a simple dynamical model of innate immunity. The analysis indicates that when an infection occurs, it triggers inflammation, which activates the innate immune system and initiates the activation cycle. Consequently, pathogens may be eradicated, leaving behind persistent chronic inflammation. Alternatively, the pathogens may not be eradicated, with their abundance either stabilizing at a positive level or oscillating indefinitely. When innate immunity is activated in the absence of inflammation, pathogens are eradicated more easily, and the likelihood of oscillations in inflammation, immune responses, and pathogen abundance is reduced.

Phase plane showing three different behaviors.

BMB Article Highlight: Joseph Baafi & Amy Hurford (2025)

Fri, 14 Mar 2025 05:59:20 GMT

Modeling the Impact of Seasonality on Mosquito Population Dynamics: Insights for Vector Control Strategies

by Joseph Baafi and Amy Hurford

Population models are tools for studying the dynamics of organisms and their interactions with the environment, but oversimplifying these models can lead to inaccurate predictions. Our research highlights this challenge by developing a model that incorporates seasonal temperature and rainfall patterns. We demonstrate how environmental factors significantly influence mosquito abundance. Neglecting these factors may lead to biased predictions, while our approach highlights regional differences in mosquito dynamics. For instance, the optimal timing, duration, and strategies for vector control may vary across regions due to differences in seasonal weather. We identified key parameters that drive model outcomes using sensitivity analysis.

Mathematical model illustrating regional variations in mosquito dynamics and peak abundance timing, emphasizing the importance of region-specific control strategies.

Winter 2025 Newsletter

Fri, 28 Feb 2025 17:22:29 GMT

Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Bryn Mawr College).

Editorial - A message from SMB President Jane Heffernan and President-Elect Reinhard Laubenbacher
News - updates from:
- SMB Subgroups
- Royal Society Publishing
People - Interview with Dr. Marissa Renardy, GSK.
Featured Figures - Micah Brush

To see the articles in this issue, click the links at the above items.

Contributing content

We welcome submissions to expand the content of the newsletter. The next issue will be released in April, so if you would like to contribute, please send an email to the editors by the start of April 2025 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the Member Forum rather than to the newsletter.

We hope you enjoy this issue of the newsletter!

Sara, Burcu, Thomas and Olivia
Editors, SMB Newsletter

Editorial

By Jane Heffernan and Reinhard Laubenbacher

The SMB was founded in 1973 to promote the development and dissemination of research and education at the interface between the mathematical and biological sciences. The SMB is an inclusive society and serves a diverse community of researchers and educators in academia, industry, and government agencies throughout the world. The SMB opposes any actions that counter its mission.

Science is currently being subjected to political, ideological and financial influence in some areas of the world, including the United States. SMB members in these regions thus are in a time of great uncertainty about the future of their research and travel funding, which will ultimately affect their ability to conduct effective, groundbreaking and impactful research, dissemination and training.

At this time, the SMB would like to reassure its members that we will be advocating for the restoration of free inquiry in science wherever such freedom is threatened.

What can members DO?

First, we need to get as much information as we can. Some excellent sources of information to consult about the situation in the United States include Research!America and the American Institute of Biological Sciences.

Second, now more than ever, members should reach out to everybody who will listen, most importantly elected representatives in local, state and federal governments, and help them understand the dramatic effects that recent administration actions are having (and will have) on research and their academic institutions. Do not assume that they know.

Finally, it is crucial for the science community to engage in outreach to the public. Please let the SMB (president@SMB.org) know what you are doing in response and what you expect SMB to do.

Sincerely,

Jane Heffernan, President

Reinhard Laubenbacher, President-Elect

News Section

By Thomas Woolley

In this issue of the News section, we highlight the updates from the SMB Subgroups and Royal Society Publishing. Read on below.

Looking for New Editors

The SMB newsletter editor roles of Thomas Woolley and Sara Loo are coming to an end in a couple of issues. If you are interested in joining the newsletter team, please send an email to woolleyt1@cardiff.ac.uk.

Upcoming Conferences

The Mathematical Biology Research Centre (MBRC) in Nepal and the Central Department of Mathematics, Tribhuvan University, are hosting the International Conference on Mathematical Biology (ICMB-2025) in Pokhara, Nepal, from June 12 to 14, 2025.

Under the theme "Quantitative Modeling and Computation in Life Sciences and Medicine," the conference will serve as a platform for a diverse community of scientists dedicated to applying mathematics to life and health sciences.

ICMB-2025 aims to showcase the event's multidisciplinary nature by uniting scholars from various fields, with a primary focus on the application of mathematical principles to biological research. The conference seeks to gather research scholars from a range of disciplines across Southeast Asia and the globe.

Please Visit:
https://sites.google.com/view/icmbnepal/home?authuser=0

SMB Subgroups Updates

Immunobiology and Infection (IMMU)

IMMU member Peter Rashkov and colleagues are co-organizing the BIOMATH2025 conference in Sofia, Bulgaria from June 15-20, 2025. There will be a Special Topic session on Mathematical Models of the Immune system in Human Disease, with topics of interest including, but not limited to within-host models of host-pathogen interactions, cancer and immunotherapy, immunity and vaccination, autoimmunity and inflammation, signaling pathways, regulatory networks, multiscale immuno-epidemiological models, etc. Registration is open until March 31, 2025.

Cell and Developmental Biology (CDEV)

CDEV Subgroup are holding two mini-symposia at the SMB Annual Meeting.

Title: From data to mechanisms: advancement in modeling in cell and developmental biology

Abstract: In many cell and developmental processes, both modeling and data analytic approaches are necessary in order to generate useful modeling predictions to guide the design of further experiments for both validating and improving biological insight. There is an increased understanding that the application of machine learning methods can also be used to enhance common data-driven modeling techniques, including parameter and equation inference, classification, and sensitivity analysis. The speakers in this session will discuss how differential equation models, stochastic models, and methods from machine learning can be combined to address questions related to cell growth, intracellular transport, cell differentiation, cell migration, and tissue development. The speakers will highlight current research progress and challenges associated with combining modeling and inference approaches in cell and developmental biology.

Royal Society Publishing

Proceedings B of the Royal Society has recently published a new special issue - "A mathematical theory of evolution": phylogenetic models dating back 100 years compiled and edited by Noah A Rosenberg, Tanja Stadler and Mike Steel and the articles can be accessed directly at https://bit.ly/PTB1919

A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org

People Section

By Sara Loo

Interview with Dr. Marissa Renardy, Associate Director of Quantitative Systems Pharmacology at GSK.

Featured Figures

By Burcu Gürbüz

In this issue, we feature the work of Micah Brush, from the University of Victoria.

Insect populations, particularly forest pests, often exhibit “eruptive dynamics”, characterized by prolonged periods of low, endemic population densities followed by sudden, large-scale outbreaks. Understanding the mechanisms that drive these transitions is critical, especially in the context of climate change, which can alter environmental conditions and affect both insect behavior and forest ecosystems. This study by Brush and Lewis focuses on the mountain pine beetle (Dendroctonus ponderosae), a species notorious for its devastating impact on North American forests. The authors develop a mechanistic model to elucidate the factors that contribute to these outbreaks and to predict how climate change may influence future dynamics.

The authors extend a previous model that integrates key aspects of mountain pine beetle biology with forest growth dynamics. The enhanced model introduces a fraction of low-vigor trees, which are more susceptible to beetle attacks. The primary components of the model include: beetle population dynamics, forest composition and climate variables.

Through analytical and numerical simulations, the study reveals several critical insights. The authors present threshold dynamics. The model identifies specific thresholds in beetle population density and forest composition that, once crossed, can trigger rapid transitions from endemic to epidemic states. Then the impact of low-vigor trees is considered. An increase in the proportion of low-vigor trees lowers the threshold for beetle outbreaks, making forests more susceptible to epidemics. Moreover, the implications of climate change are taken into account. Climate-induced stressors, such as increased temperatures and prolonged droughts, can elevate the proportion of low-vigor trees and enhance beetle survival and reproduction rates, thereby increasing the frequency and severity of outbreaks.

Brush and Lewis’ study advances our understanding of the drivers of insect outbreaks and highlights the critical role of climate change in shaping future dynamics. The mechanistic model provides a valuable tool for predicting potential outbreaks and informing management practices to mitigate pest impacts on forest ecosystems.

Figure: Comparison of the fixed points in the model with no low-vigor trees (f=0), with only low-vigor trees (f=1), and with a small number of low-vigor trees (f=0.1). Figure 1 demonstrates graphically how these fixed points arise. It illustrates the structure of the model, detailing the interactions between beetle populations, tree vigor, and environmental factors. This schematic is critical to understanding the basic assumptions and components of the model.

BMB Article Highlight: Alejandro F. Villaverde (2025)

Wed, 26 Feb 2025 07:33:31 GMT

Employing observability rank conditions for taking into account experimental information a priori

by Alejandro F. Villaverde

A dynamic model is identifiable if it is possible to infer its parameters by measuring its output over time. Likewise, it is observable if it is possible to determine its state variables in the same way. Since parameters can be treated as constant state variables, identifiability can be considered as a particular case of observability. Thus, both properties can be analysed by building an observability matrix and checking whether it has full rank. This test can be performed before collecting experimental data (i.e., “a priori”), and it may reveal structural issues of the model equations. Here we explore whether such a test can be extended to assess the influence of experimental characteristics, including the number of experiments.

Left: noiseless simulation of the model output (black line) and artificial noisy data (red circles) used for parameter estimation. Right: bootstrap results for the estimation of one of the model parameters. It can be seen that the parameter can be estimated accurately, despite the difficulty of determining high order derivatives of the output measurements.

Biology in Numbers- Episode 2.6: Mark Lewis

Wed, 12 Feb 2025 19:08:35 GMT

…where we talk: the Akira Okobu prize, the Fokker-Planck equation, and the movement of bears.

Mark Lewis is a mathematical ecologist at the University of Victoria. He uses mathematical models to understand the environment and our human impacts. He tries to maintain that work life balance by spending that hard-earned free time curling.

Find out more about Mark’s groups’ work on the following website: https://lewisresearchlab.org/.

Find out more about SMB on:

BMB Article Highlight: Prajakta Bedekar, Rayanne A. Luke, and Anthony J. Kearsley (2025)

Thu, 06 Feb 2025 09:47:28 GMT

Prevalence Estimation Methods for Time-Dependent Antibody Kinetics of Infected and Vaccinated Individuals: A Markov Chain Approach

by Prajakta Bedekar, Rayanne A. Luke, and Anthony J. Kearsley

Modeling the change in antibody levels post infection or vaccination improves understanding of the time-dependent immune response. Disease or vaccination prevalence in populations and time-dependence simultaneously affect antibody levels, interact non-trivially, and pose considerable modeling challenges. We model transitions from the naïve state to either the infected or vaccinated state using a time-varying stochastic process. This is coupled with a probabilistic framework to describe post-event antibody dynamics. An important result of this work is the design of an unbiased prevalence estimation method. This is a critical step towards analyzing protection from infection or vaccination and improving booster timing recommendations.

Graphical abstract created with bioRender.

BMB Article Highlight: Marine A. Courtois et al. (2025)

Wed, 29 Jan 2025 15:19:41 GMT

How Residual Fertility Impacts the Efficiency of Crop Pest Control by the Sterile Insect Technique

by Marine A. Courtois, Ludovic Mailleret, Suzanne Touzeau, Louise van Oudenhove, and Frédéric Grognard

The sterile insect technique (SIT) is a pest control method. It reduces pest populations through the release of sterilized males that disrupt reproduction by preventing females from producing viable offspring. Our study examines how residual fertility—when sterilized males retain some fertility—affects SIT success. Using mathematical models, we identified residual fertility thresholds: (1) below which pest eradication is achievable, and (2) below which only population reduction can be obtained. This research enhances SIT implementation strategies by providing insights into the balance between residual fertility and sterile male attractiveness. These findings help develop stronger pest control strategies for sustainable agriculture.

Optimizing sterile insect technique (SIT): managing residual fertility.

BMB Article Highlight: Sarah Vollert et al. (2025)

Wed, 15 Jan 2025 10:06:40 GMT

Ecosystem knowledge should replace coexistence and stability assumptions in ecological network modelling

by Sarah Vollert, Christopher Drovandi, and Matthew Adams

Ecosystem models are often used to aid conservation decision making, to help quantify the risks of management, and assess the probability of conservation success. But these models are frequently built on the assumption that an ecosystem will naturally stabilise towards a coexisting balance of species. This paper argues that this theoretical assumption is inappropriate for conservation planning, because it downplays the risks of extinction. Instead, we demonstrate how ecological field knowledge can replace this assumption without significant loss of information and show that expert knowledge leads to more realistic population predictions.

Using ecological observations as an alternative for constructing ecosystem models.

BMB Article Highlight: Vivienne Leech et al. (2025)

Thu, 09 Jan 2025 00:48:22 GMT

A dynamical analysis of the alignment mechanism between two interacting cells

by Vivienne Leech, Mohit P. Dalwadi, and Angelika Manhart

In biology, organisms often align their body orientation to coordinate their movement. Famous examples are schools of fish or flocks of birds. Here we focus on aligning cells, such as bacterial cells or skin cells, whose collective dynamics affects the behaviour of the bacterial colony or the properties of the skin tissue (relevant e.g. in scar formation). We zoom into the collective alignment dynamics and focus on the interactions between two cells on a 2D surface. The cells move, turn and deform in order to avoid overlapping. We thoroughly mathematically analyse the resulting non-linear system of ordinary differential equations. This allows to understand the role the model ingredients, such as self-propulsion, play for alignment dynamics.

Mathematically analysing cell alignment.

BMB Article Highlight: Zhenying Chen et al. (2024)

Wed, 01 Jan 2025 13:48:15 GMT

Dynamics of Antibody Binding and Neutralization during Viral Infection

by Zhenying Chen, Hasan Ahmed, Cora Hirst, and Rustom Antia

During a viral infection, virions are continuously produced by infected cells and rapidly decay. Meanwhile, neutralizing antibodies are produced and bind to virion sites, preventing them from infecting target cells. In this context, virus growth rate and decay rate have an impact on the amount of antibody binding, potentially substantially reducing the impact of Koff on antibody binding. We then show that greatly simplified neutralization models have similar virus growth dynamics to more complex model, but they are less suited for exploring how antibody affinity and the proportion of bound sites on a virion reduce virus growth rate. Thus, the choice of models should depend on the specific research question of interest.

Graphical abstract created with bioRender.

Biology in Numbers- Episode 2.5: Suzanne Sindi

Thu, 19 Dec 2024 01:45:19 GMT

…where we talk: society nominations, prion proteins and murderbots.

Professor Suzanne Sindi is a Mathematical Biologist studying protein aggregation, and blood coagulation through modeling and data science. She is passionate about promoting inclusion in math and STEM, and was inspired to go into science by dinosaur-related Sci-Fi.

Find out more about Suzanne’s work on her website: https://www.sindilab.com/.

If you feel inspired to step up, you can learn more about nominations for SMB positions by emailing: nominations@smb.org

Find out more about SMB on:

BMB Article Highlight: Ruibo Zhang & Ivana Bozic (2024)

Wed, 11 Dec 2024 07:03:15 GMT

Accumulation of Oncogenic Mutations During Progression from Healthy Tissue to Cancer

by Ruibo Zhang and Ivana Bozic

Assessing the Role of Patient Generation Techniques in Virtual Clinical Trial Outcomes

Carcinogenesis is a multi-stage process in which driver gene mutations occur sequentially. Understanding the arrival times of genetically different subclones provides important insights into tumorigenesis. In this work, we establish a multi-type branching process to model the initiation of cancer that starts from a healthy tissue in homeostasis. Mutations can be either neutral or advantageous, which reflects that inactivating a single copy of a tumor suppressor gene does not directly provide a selective growth advantage. We approximate the distribution of the arrival time for each type and compare it to computer simulations of the process. The results are applied to study the initiation of colorectal cancer and chronic myeloid leukemia.

Model illustration. The model describes an evolutionary process that starts with a large healthy population in homeostasis (blue circles). Mutations that are either neutral or advantageous occur sequentially, which causes subsequent types to be either homeostatic (yellow) or initiated (orange). The cancerous type (red) emerges only when all the required genetic alterations have taken place.

Autumn 2024 Newsletter Part 2

Fri, 06 Dec 2024 20:45:58 GMT

Editorial

By Sara Loo

Ways to engage with SMB

This quarter’s editorial is less an editorial, and more of a spiel of a couple of ways in which you can engage with the Society and share with others in the community! We love hearing from our community and looking for ways in which to engage with one another.

As a member of SMB, you have access to our Member Forum, news items, and can share your work and interests with others through our Highlights page. If you haven't logged on for a while, now might be a good time to make sure your profile is up to date with your latest interests - click here to update and select your preferred Subgroups to receive communications from subgroup leaders.

SMB Member Forum

A primary way you can do this is through the SMB Member Forum. The forum is a great platform for sharing with others in our community – be it an upcoming conference, job postings, funding opportunities, or even a call-out for like-minded members to collaborate.

On the main website, recent member forum posts can be seen on the Home page, as well as through the Communications tab.

If you are a member of SMB, once you are logged on to the main website, post on our Member Forum by clicking on Create Topic and including any details you want to share.

Click on Subscribe to get updates on all new posts via email. You can also subscribe to a single forum post for updates to that specific post.

For any membership issues or problems with logging on to the website, contact website@smb.org

Highlights

In addition to the forum, if you have a paper published in the Bulletin of Mathematical Biology that you would like to highlight, our publications team would like to hear from you! Submit the paper to the team to highlight, using the linked form in the website menu, with a brief description (max 750 words) of the highlights of your paper, along with a figure. Think of this as a brief ‘featured figure’! These get posted by the Publications Team in the News section of our website.

Bluesky

Have you found yourself in the recent wave drifting over to Bluesky? You can find us at @smbmathbiology.bsky.social where we share recent paper highlights, repost job advertisements, and other recent news. We’ve also pulled together an SMB Starter Pack so you can follow all your favorite mathematical biologists and continue to grow our community.

Other social media

X: @SMB_MathBiology
Instagram: @smbmathbio
Threads: @smbmathbio

Featured Figures

By Thomas Woolley

In this issue, we feature the work of Jana Gevertz, College of New Jersey, and Giulia Celora, University College London.

We asked Jana Gevertz to tell us a bit more about her work here:

Clinical trials are research studies where novel medical interventions are tested on people who volunteer to receive the treatment of interest. These studies are the primary way that researchers find out if a new treatment is safe and effective in humans. The predictions made by clinical trials are generally limited by small sample sizes and may be biased to certain demographic groups which are more inclined to enroll in these studies.

Virtual clinical trials (VCTs), grounded in data-informed mathematics models, are growing in popularity as a tool for quantitatively predicting heterogeneous treatment responses across a population. They hold the promise of complementing standard clinical trials by computationally permitting the analysis of a more diverse and representative patient population. In the context of a VCT, a “plausible patient” is an instance of a mathematical model with parameter (or attribute) values chosen to reflect features of the disease and response to treatment for that particular patient. A challenging question in the design of VCTs is to determine which set of model parameterizations (that is, which “plausible patients”) should actually be included in the virtual population.

The aim of our work was to rigorously quantify the impact that VCT design choices have on the heterogeneity of the virtual population, and on the predictions of a virtual clinical trial. To isolate the impact of VCT design choices, we worked with simulated patient data and a simple, toy model of tumor growth that predicted response to the treatment. In this controlled setting, we studied the impact of the following VCT design choices (see Figure): the prior distribution of each parameter that varies across patients, and the method for selecting which parameterizations are considered virtual patients and thus included in the VCT. Our analysis revealed that the prior distribution, rather than the inclusion/exclusion criteria, has a larger impact on the heterogeneity of the virtual population. Yet, the predictions of the virtual clinical trial were more sensitive to the inclusion/exclusion criteria utilized. This foundational understanding of the role of virtual clinical trial design should help inform the development of future VCTs that use more complex models and real data.

We asked Giulia Celora to tell us a bit more about her work here:

Characterising Cancer Cell Responses to Cyclic Hypoxia Using Mathematical Modelling

In solid tumours, the presence of regions of abnormally low oxygen levels (i.e., hypoxia) is recognised as a major driver of tumour progression and therapeutic resistance. Even though in vitro models of hypoxia exist, they often fail to capture the complex and heterogeneous oxygenation dynamics of real tumours. While most experimental studies have focussed on characterising cell responses to constant hypoxic conditions, in vivo observations show that tumour oxygen levels can fluctuate on fast timescales and expose cancer cells to periodic cycles of hypoxia; a phenomenon known as cyclic hypoxia. These observations raise questions regarding the applicability of such experimental findings to the clinical understanding of hypoxia: do cyclic and constant hypoxia elicit different responses in cancer cells? If so, what features of fluctuating oxygen conditions are cancer cells sensitive to? Is the frequency of hypoxia cycles, their duration? Or both?

In our recent publication, we used mechanistic mathematical modelling to quantify the impact of prolonged exposure to various cyclic hypoxia conditions on the population growth and survival of tumour cell cultures. In particular, we developed a structured stochastic individual-based cell cycle model that accounts for hypoxia-driven dysregulation of both cell cycle and cell survival. In this framework, each cell is an agent that can either proliferate or die with probabilities that depend on its internal state. The cell internal state is described by a list of categorical and continuous structure variables, that also evolve probabilistically over time. Structure variables allow us to capture the multi-layered feedback between oxygen levels, intracellular processes (such as DNA replication and repair), and cell fate – namely, proliferation and death.

Our model allows us to efficiently characterise how cancer cells respond to hypoxia cycles of varying duration and frequency. As shown in the Figure, we find that cell responses to cyclic hypoxia can be classified into four major groups depending on the extent to which population growth and cell survival are affected by periodic exposure to hypoxia. Our results highlight the multifaceted nature of cyclic hypoxia and the role of fluctuating oxygen levels in creating heterogeneous environmental conditions within tumours. You can learn more about our work and the implications of our results on the connection between cyclic hypoxia and intra-tumour heterogeneity here:

Autumn 2024 Newsletter Part 1

Fri, 06 Dec 2024 20:37:55 GMT

Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Bryn Mawr College).

News - updates from:
- SMB Subgroups
- Royal Society Publishing
People - Interview with Dr Hao Wang, University of Alberta.
Editorial - Engaging with the SMB Community
Featured Figures -
- Jana Gevertz
- Giulia Celora

To see the articles in this issue, click the links at the above items.

Contributing content

We welcome submissions to expand the content of the newsletter. The next issue will be released in January, so if you would like to contribute, please send an email to the editors by the start of January 2025 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the Member Forum rather than to the newsletter.

We hope you enjoy this issue of the newsletter!

Sara, Burcu, Thomas and Olivia
Editors, SMB Newsletter

News Section

By Olivia Chu

In this issue of the News section, we highlight the updates from the SMB Subgroups and Royal Society Publishing. Read on below.

Engage in innovative mathematical biology research at the NSF-Simons National Institute for Theory and Mathematics in Biology

Random Dynamical Systems, with Applications in Biology workshop held in November 2024

The NSF-Simons National Institute for Theory and Mathematics in Biology (NITMB) was founded in 2023, with its mission being to enhance integration of research in the mathematics and biology disciplines. The overall vision of the NITMB is to understand the mathematical basis of constraints that drive biological capabilities. Achieving this goal promises to transform biological research and to inspire new mathematical discoveries. Funded by the U.S. National Science Foundation and the Simons Foundation, NITMB operates as a working partnership between Northwestern University and the University of Chicago. NITMB is located on the 35th floor of the John Hancock Center at 875 N. Michigan Avenue in downtown Chicago. It is located halfway between the Northwestern University campus in Evanston and the University of Chicago campus in Hyde Park. NITMB has a dedicated auditorium for convening activities, a dining area, temporary offices for visitors, and extensive open collaborative work spaces for research and interaction. The Institute is designed to house most of its research and convening activities, and it is readily accessible to participants from across the U.S. and the world.

Researchers at the Institute generate new mathematical results and uncover the “rules of life” through theoretical studies, data-informed mathematical models, and various computational and statistical tools. The structure of NITMB-supported research allows theorists and experimentalists to collaborate on experimental design, data analysis, and modeling. NITMB also fosters the development of new mathematics that is inspired by biology. In particular, the Institute offers two forms of research support: (i) funding for research projects and (ii) funding to visit and perform research at NITMB. Scientific conferences, workshops, and long programs hosted by NITMB are organized around broad conceptual themes that are common in both mathematics and biology; they also highlight opportunities to develop new mathematics. These events are open to participants from institutions across the world and include researchers in both mathematics and biology.

Stay up to date with the latest information about NITMB by visiting nitmb.org.

SMB Subgroups Updates

Population Dynamics, Ecology, and Evolution (PDEE)

The PDEE subgroup successfully launched an online journal club. We are seeking presenters and article suggestions; we are particularly interested in participation from scholars in the global South. To learn more, email subgroup chair Judith Miller at Judith.Miller@georgetown.edu.

Mathematical Epidemiology (MEPI)

The Mathematical Epidemiology (MEPI) subgroup had a wonderful time at the annual meeting in Korea. We held a session on Infectious Disease Modeling Across Time, Space, and Scale. Speakers included Soyoung Park, Edward Hill, Stacey Smith?, Folashade Agusto, Sunhwa Choi, Camelia Rose Walker, and Tin Phan.

We also wish to share that our current officers are Meredith Greer (Chair) and Prashant Kumar Srivastava (Co-Chair), along with Michael Robert (Past Chair).

Cardiovascular Modeling

Committee membership update: we now have Mitchell Colebank at University of South Carolina joining our committee as Secretary in addition to Michael Watson and Vijay Rajagopal as President and Vice President. We will be growing our committee membership in 2025 to adequately represent our growing member community.
We have a website which we would love to populate with CVM subgroup member stories and publications, please email one of the committee members to let us know.
We have also created a LinkedIn page that we encourage our members to join. Get immediate access to your network of colleagues for your next collaboration, next job search or next recruit into your team.
If you would like to get involved with our community please make sure you register your membership with CVM when you renew membership or become a new member of SMB.
Look out for an email from us when SMB2025 opens up proposals for minisymposia.

Mathematical Oncology

Fields Thematic Program in Mathematical Oncology, July - December 2024
Over the past 20 years the mathematical modelling of cancer has developed from a side discipline to centre stage. Many modern treatment developments are accompanied by mathematical and computational modelling. For example, optimal radiation schedules are computed based on tumor control probabilities, glioma treatment is guided by medical image processing, and evolutionary adaptive therapies are guided by mathematical modelling. In fact, all aspects of the seminal “Hallmarks of Cancer” from Hanahan and Weinberg (2000 and 2010) have now been modelled with mathematical and computational models. The well structured and uncompromisingly rigorous methods of mathematical modeling has a lot to offer for future developments in cancer research and treatments. Not only does it guide researchers in the right direction, it also, unceremoniously, tells us when something does not work, and why. In support of research activities in this very active area of applied mathematics, the Thematic Program in Mathematical Oncology has been hosted at the Fields Institute from July to December 2024. The thematic program has featured a large number of activities, including six workshops, two Fields postdocs, several long term visitors, and over 250 short term visitors. It has also hosted three distinguished visitors (N. Komarova, H. Byrne, T. Hillen) and offered a mathematical oncology graduate course. For details and videos of many of the talks, please see: http://www.fields.utoronto.ca/activities/24-25/oncology
Math Oncology Interviews
Thomas Hillen started an interview series on youtube, where he invites experts in mathematical oncology for a short interview to find out who they are, what career path they had, and what motivates them. These informal conversations are fun to watch and allow younger scientists to meet some of the leaders in the field. Check it out: https://www.youtube.com/@MathOncologyInterviews/playlists
Workshop on Uncertainty Quantification
One of your MathOnco co-chairs is also co-organizing an ICERM workshop on Uncertainty Quantification for Mathematical Biology, where many SMB members will participate. All are welcome to apply: https://icerm.brown.edu/program/topical_workshop/tw-25-uqmb

Cell and Developmental Biology

The Cell and Developmental Biology (CDEV) subgroup elected new officers this fall:

Chair: Keisha Cook (Clemson University, keisha@clemson.edu)

Secretary: Anna Nelson (Duke University, anelson@math.duke.edu)

Committee members:

Alessandra Bonfanti (Politecnico di Milano, bonfantiale.ab@gmail.com)
Giulia Celora (University College London, g.celora@ucl.ac.uk)
Kelsey Gasior (University of Notre Dame, kgasior2@nd.edu)
Qixuan Wang (University of California, Riverside qixuan.wang@ucr.edu)

Royal Society Publishing

Journal of the Royal Society Interface celebrates its 20th anniversary!

On 22nd November 2004, J. R. Soc. Interface was launched to provide a home for cross-disciplinary science at the boundary of the life and physical sciences. To mark its 20thanniversary, we are looking back on the landscape of interdisciplinary science two decades ago and looking forward to what the future may hold.

As part of our celebrations, you are invited to write a Perspective on where you think this field will be in 20 years’ time, with a £1000 on offer. We also have interviews with our past and present editors, as well as a blog post with our Senior Publishing Editor, and a collection of new reviews and historic research.

Tree frog (Litoria caerulea). Credit: iStock.com / jamcgraw.

People Section

By Burcu Gürbüz

Interview with Dr Hao Wang, University of Alberta, an organizer for next year's SMB Annual Meeting.

BMB Article Highlight: Louis V. Kunz et al. (2024)

Mon, 02 Dec 2024 19:12:18 GMT

A coupled spatial-network model: A mathematical framework for applications in epidemiology

by Louis V. Kunz, Jesús J. Bosque, Mohammad Nikmaneshi, Ibrahim Chamseddine, Lance L. Munn, Jan Schuemann, Harald Paganetti, and Alejandro Bertolet

AMBER (Agent-based fraMework of radioBiological effects of Radiotherapy) simulates tumor growth, vasculature, and radiation response by combining agent-based modeling (ABM) with Monte Carlo (MC) methods. Using a hybrid approach and voxelated geometry it tracks tumor and microenvironmental changes over time, including oxygen levels and VEGF at a mesoscopic scale, allowing for facilitated comparison with MRI and CT. The inclusion of multifactorial biological determinants allows AMBER to represent tumor growth and response to radiotherapy in a relevant manner, with for example the appearance of a necrotic core. The modular implementation of the framework allows for easy extension and refinement to specific applications.

Evolution of the distribution of alive and necrotic cells in a central slice of a tumor grown with AMBER, along with the evolution of the vasculature, from low density in purple to high density in yellow. Third row shows the micro vessel density, with well oxygenated voxels in blue and hypoxic/anoxic voxels in orange/red. Last row shows the explicit vasculature, with only healthy vasculature in the first column and new vessels growing due to angiogenesis in the next columns.

BMB Article Highlight: Hannah Kravitz et al. (2024)

Wed, 20 Nov 2024 07:50:06 GMT

A coupled spatial-network model: A mathematical framework for applications in epidemiology

by Hannah Kravitz, Christina Durón, and Moysey Brio

A new compartmental modeling framework is proposed which couples population centers at the vertices, 1D travel routes on the edges, and a 2D continuum containing the rest of the population to simulate how an infection spreads through a population. The edge equations are coupled to the vertex ODEs through junction conditions, while the domain equations are coupled to the edges through boundary conditions. The model is illustrated on some example geometries, and a parameter study example is performed. The observed solutions exhibit exponential decay after a certain time has passed, and the cumulative infected population over the vertices, edges, and domain tends to a constant in time but varying in space, i.e., a steady state solution.

Example implementation of the coupled spatial-network model.

BMB Article Highlight: John T. Nardini (2024)

Wed, 13 Nov 2024 20:33:14 GMT

Forecasting and Predicting Stochastic Agent-Based Model Data with Biologically-Informed Neural Networks

by John T Nardini

https://systemsmedicine.pulmonary.medicine.ufl.edu/

Agent-based models (ABMs) are widely used to study biological systems, but heavy computational requirements limit our ability to predict their behavior. Differential equation (DE) models are often used as ABM surrogates, but they can provide poor predictions. We propose that biologically-informed neural networks (BINNs) can learn informative DE models that predict ABM behavior. We demonstrate how BINNs’ learned DE models can forecast future ABM data at new parameter values. We highlight the strong performance of this methodology in three case study ABMs that explore different rules on cell-cell interactions in collective migration. BINNs learn predictive and interpretable DE models even when other DE models are ill-posed or complex.

1) We explore several different ABM rules and summarize the ABM density over time. 2) BINN models can be trained to the ABM data. 3) We predict new ABM data by simulating the BINN's learned PDE model.

Biology in Numbers- Episode 2.4: Matthew Penn

Thu, 07 Nov 2024 01:27:13 GMT

…where we talk about a paper studying who and when we should vaccinate.

After completing a DPhil in Statistics from the University of Oxford, focussing in epidemiology and phylogenetics, Matt now works as a data scientist for Italian football club Como 1907.

Matt was awarded the Lee A. Segel Prize for Best Student Paper published in The Bulletin of Mathematical Biology for his paper Asymptotic Analysis of Optimal Vaccination Policies.

Join us to learn more about how this paper can help health professionals better assess the best way to distribute vaccines.

Find out more about Matt and his work on Linkedin:
linkedin.com/in/matthew-penn-732551232/

Find out more about SMB on:

Apple Link Spotify Link Read the full transcript

Biology in Numbers- Episode 2.3: Reinhard Laubenbacher

Wed, 30 Oct 2024 18:18:08 GMT

…where we talk parasites, motorbikes, and digital twins.

Professor Reinhard Laubenbacher is: the Director of Laboratory for Systems Medicine at the University of Florida, an AAAS fellow (American Association for the Advancement of Science), and a scientist interested in using math to understand human disease and more specifically fungal infections in the lungs. When not at work, Reinhard and his wife enjoy motorbiking everywhere from the swamps of Florida, to the plains of Patagonia.

Find out more about Reinhard’s work on the following websites:

https://systemsmedicine.pulmonary.medicine.ufl.edu/profile/laubenbacher-reinhard/

Find out more about SMB on:

BMB Article Highlight: Stefano Pasetto et al. (2024)

Wed, 23 Oct 2024 21:49:07 GMT

Harnessing flex point symmetry to estimate logistic tumor population growth

by Stefano Pasetto, Isha Harshe, Renee Brady-Nicholls, Robert A. Gatenby, Heiko Enderling

Tumor growth dynamics are well-described mathematically by the S-shaped logistic function. Initially exponential growth decelerates as the tumor approaches its carrying capacity – the maximum tumor burden that can be sustained by the local and systemic (micro-)environment. The volume-to-carrying capacity ratio is a major determinant of response to (radio-)therapy; therefore, it is of high importance to estimate the carrying capacity from limited tumor volume measurements. The symmetry around the logistic growth flex point can be used to introduce ghost points symmetric to observed data points to double the available data to calibrate model parameters for an individual patient. With this approach, fewer data points are necessary to identify patient-specific carrying capacities, thereby potentiating shorter times to treatment decisions.

BMB Article Highlight: Bernadette J. Stolz et al. (2024)

Fri, 18 Oct 2024 19:53:52 GMT

Relational Persistent Homology for Multispecies Data with Application to the Tumor Microenvironment

by Bernadette J. Stolz, Jagdeep Dhesi, Joshua A. Bull, Heather A. Harrington, Helen M. Byrne, Iris H. R. Yoon

State-of-the-art data is exquisite in detail, often containing information on multiple species, e.g. cell types in imaging data. However, there are very few techniques equipped to analyse and quantify relations in such data. The paper by Stolz, Dhesi et al. proposes two topological approaches for multispecies data that can encode relations in spatial data. The authors showcase the methods on synthetic data of the tumour microenvironment which models the behaviour and interactions between tumour cells, macrophage subtypes, necrotic cells, and blood vessels. They demonstrate that relational topological features can extract biological insight, including dominant immune cell phenotype and parameter regimes of the data-generating model.

Relational persistent homology encodes spatial relations in multispecies data. We use synthetic images of the tumour microenvironment generated by an agent-based model as input to two different topological methods for encoding relations: Dowker persistent homology (top row) and multispecies witness persistent homology (bottom row). The topological features that we extract can classify the synthetic images according to dominant immune cell type and cluster qualitative behaviours of the model.

BMB Article Highlight: Jana L. Gevertz & Joanna R. Wares (2024)

Wed, 09 Oct 2024 19:13:43 GMT

Assessing the Role of Patient Generation Techniques in Virtual Clinical Trial Outcomes

by Jana L. Gevertz and Joanna R. Wares

Virtual clinical trials (VCTs) are a tool for understanding heterogeneous treatment responses. A number of techniques have been proposed to determine the set of model parametrizations ("virtual patients") that get included in a VCT. There is, however, no standard way to set the parameter prior distributions and to choose the criteria for including or excluding a parametrization sampled from the priors in the plausible population. In this work, we rigorously quantify the impact that VCT design choices have in a controlled setting using simulated patient data and a toy mathematical model. Our study provides a foundational understanding of how these choices influence the heterogeneity of virtual populations, and the predictions of a VCT.

Schematic of two methods for the generation of plausible patients for a virtual clinical trial.

Biology in Numbers - Episode 2.2: Professor Stacey Smith?

Tue, 01 Oct 2024 15:21:24 GMT

...where we talk about infectious diseases, mentorship and mathematical tattoos.

Professor Stacey Smith? is an infectious disease modeler who appreciates the real world impacts that math biology can have. She leads educational and mentorship programming at the SMB and apparently never says no to anything SMB related. We caught Stacey at SMB 2024 in South Korea to talk about her research, life-changing transitions, and being a Whovian.

Check out Stacey’s website for science, articles and Sci-Fi nerdiness: mysite.science.uottawa.ca/rsmith43/

And for those curious about the tattoo, read more about the Mandlebrot set: wikipedia.org/wiki/Mandelbrot_set

Find out more about SMB on:

Biology in Numbers - Episode 2.1: SMB 2024

Thu, 26 Sep 2024 15:28:09 GMT

…where we talk all things math bio at the annual meeting.

Science isn’t complete until it’s communicated, and what better place to do this than a scientific conference. This year, more than a thousand scientists were lucky enough to attend the SMB meeting in Seoul in Korea. This special episode gives a brief preview of some of the exciting research being done, as well as the people doing the work. Join us to hear from:

Fred Adler - Professor at the University of Utah, Utah, US
Kit Gallagher - Doctoral student at the University of Oxford, US & Moffitt Cancer Center, Florida, US
Megan Greischer - Assistant Professor at Cornell University, New York, US
Jona Kayser - Group leader at the Max Planck Institute for Physics and Medicine, Erlangen, Germany
Bo-Moon Kim - Doctoral student at Kyoto University, Kyoto, Japan
Breanne Sparta - Postdoctoral Researcher at UCLA, Los Angeles, US
Rossana Vermiglio - Full professor at the University of Udine, Udine, Italy.

Find out more about SMB on:

BMB Article Highlight: Yonatan Ashenafi and Peter R. Kramer (2024)

Thu, 19 Sep 2024 09:00:36 GMT

Statistical Mobility of Multicellular Colonies of Flagellated Swimming Cells

by Yonatan Ashenafi and Peter R. Kramer

Eukaryotic cells, such as protozoa and sperm, use flagella—whip-like structures—for movement, helping them navigate, find food, interact, and evade predators. Researchers study flagellar propulsion through fluid dynamics and cellular responses. Recently, attention has shifted to multicellular colonies, where each cell has its own flagellum. In these colonies, misaligned flagella can cause unique movements, like rotating or spiraling. This paper presents a mathematical model to predict how flagellar behavior and colony structure affect movement, offering insights into the emergence of functional multicellularity.

Time-lapse composite schematic of a circular colony's planar motion. The colony consists of a dozen flagellated cells.

BMB Article Highlight: Dionn Hargreaves et al. (2024)

Thu, 12 Sep 2024 14:20:18 GMT

Relaxation and Noise-Driven Oscillations in a Model of Mitotic Spindle Dynamics

by Dionn Hargreaves, Sarah Woolner, and Oliver E. Jensen

Cell division orientation is controlled by the mitotic spindle, which dynamically positions itself to segregate chromosomes. Often, spindle positioning shows noisy, non-linear oscillations, observed here in dividing embryonic epithelial cells. These oscillations are thought to result from molecular motors that randomly attach, walk along, and detach from spindle microtubules. Prior models predict 1D spindle oscillations, but the effects of noise and nonlinearity remain underexplored. We demonstrate that relaxation oscillations emerge when pulling dominates restoring forces provided by flexible microtubules. Stochastic simulations and analysis reveal noise-induced oscillations, offering new insights into oscillation mechanisms.

Force generators (molecular motors) attach, walk along, and detach from microtubules to dynamically position the spindle pole, to give rise to noise-induced oscillations.

Summer 2024 Newsletter (Part 2)

Thu, 05 Sep 2024 14:11:15 GMT

Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Bryn Mawr College).

News - updates from:
- SMB Subgroups
- Royal Society Publishing
People - Interview with new editor Olivia Chu.
Editorial - After a productive summer - About the SMB and ECMTB Conferences
- ECMTB 2024 - Burcu Gürbüz
- KSMB-SMB 2024 - Ryan Murphy, University of Melbourne
Featured Figures - SMB Poster prize winners
- Luke Heirene
- Yuan Yin

To see the articles in this issue, click the links at the above items.

Contributing content

We welcome your submissions to expand the content of the newsletter. The next issue will be released in late October, so if you would like to contribute, please send an email to the editors by the start of October 2023 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the SMB digest rather than to the newsletter.

We hope you enjoy this issue of the newsletter!

Sara, Burcu, Thomas and Olivia

Editors, SMB Newsletter

Featured Figures

By Olivia Chu

In this issue, we feature the work of Luke Heirene, a graduate student at the University of Oxford, and Yuan Yin, a graduate student at the University of Oxford, who were both poster prize winners at this year’s SMB Annual Meeting.

We asked Luke to tell us a bit more about his work here:

Immunotherapies have seen success in a variety of diseases, including cancer. An important class of immunotherapy are monoclonal antibodies (mAbs). Mabs can induce their anti-tumour effects in a variety of ways. For example, they can inhibit a tumour cell’s ability to downregulate the immune response against it as well as target and stimulate immune effector cells to kill the tumour cell. Regardless of a mAbs mechanism of action, core to their effect are their interactions with target antigens. Processes that alter the ability of a mAb to bind its target antigen, such as differences in binding affinity or antigen expression, will directly impact the resulting therapeutic effect.

In our work, we use an ODE model of bivalent antibody-antigen binding to establish the key parameters that drive mAb potency and efficacy. We utilise a global parameter sensitivity analysis to establish the parameters that most affect antigen occupancy and bound antibody number, key drivers of mAb potency and efficacy, finding that the most important parameters change with antibody dose. Another key mAb-antigen interaction is the observed increase in binding affinity due to a mAb binding multiple antigens, termed the avidity effect. We use our model to predict antibody binding affinities and antigen expression numbers which result in a large avidity effect. Our results can be used to identify key parameters and interactions that can assist in the preclinical development of mAb therapeutics.

Figure caption:

(A) Schematic of model for bivalent mAb-antigen binding (Created with https://www.biorender.com)

(B) Total order Sobol sensitivity analysis for antigen occupancy as antibody concentration varies on the x-axis.

(C) Heatmaps displaying the avidity effect as measured by a change in the EC50 between a monovalent and bivalent antibody for different receptor expressions (r_tot) and binding affinities (K_D). The EC50 was calculated as the concentration at which half of the maximum bound antibody number was achieved.

We asked Yuan to tell us a bit more about her work here:

‘Accurate stochastic simulation algorithm for multiscale models of infectious diseases’ by Yuan Yin (University of Oxford), Jennifer A. Flegg (University of Melbourne), Mark B. Flegg (Monash University)

In the infectious disease literature, significant effort has been devoted to studying dynamics at a single scale. For example, compartmental models describing population-level dynamics are often formulated using differential equations. In cases where small numbers or noise play a crucial role, these differential equations are replaced with memoryless Markovian models, where discrete individuals can be members of a compartment and transition stochastically. Classic stochastic simulation algorithms, such as Gillespie's algorithm and the next reaction method, can be employed to simulate from these Markovian models exactly. The intricate coupling between models at different scales underscores the importance of multiscale modelling in infectious diseases.

However, several computational challenges arise when the multiscale model becomes non-Markovian. In this study, we address these challenges by developing a novel exact stochastic simulation algorithm. We apply it to a showcase multiscale system where all individuals share the same deterministic within-host model while the population-level dynamics are governed by a stochastic formulation. We demonstrate that as long as the within-host information is simulated at a reasonable resolution, the novel algorithm we develop will always be accurate. Moreover, the novel algorithm we develop is general and can be easily applied to other multiscale models in (or outside) the realm of infectious diseases.

Figure Caption:

(a). Sample numerical solution of the within-host CC*V (target cell-limited) model. (b). Viral dynamics for 5 individuals with different calendar infection dates. (c). Propensity of infection per susceptible. (d). Population-level dynamics. Our algorithm (Algo. 2) is compared with an approximate time-driven algorithm (Algo. 1) and a golden-standard exact algorithm (GS). (e). Accuracy comparison between Algo. 1 and Algo. 2 given different population sizes. The markers denote the maximum time resolution where the relative errors are below 5%.

Summer 2024 Newsletter (Part 1)

Thu, 05 Sep 2024 13:59:28 GMT

Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Bryn Mawr College).

News - updates from:
- SMB Subgroups
- Royal Society Publishing
People - Interview with new editor Olivia Chu.
Editorial - After a productive summer - About the SMB and ECMTB Conferences
- ECMTB 2024 - Burcu Gürbüz
- KSMB-SMB 2024 - Ryan Murphy, University of Melbourne
Featured Figures - SMB Poster prize winners
- Luke Heirene
- Yuan Yin

To see the articles in this issue, click the links at the above items.

Contributing content

We hope you enjoy this issue of the newsletter!

Sara, Burcu, Thomas and Olivia
Editors, SMB Newsletter

News Section

By Sara Loo

In this issue of the News section, we highlight the updates from the SMB Subgroups and Royal Society Publishing. Read on below.

SMB Subgroups Update

Mathematical Neuroscience Subgroup

The SMB Mathematical Neuroscience subgroup was actively engaged at the 2024 SMB annual meeting held at Konkuk University in Seoul, Republic of Korea. The event featured posters, contributed talk sessions, and mini-symposiums covering a diverse range of topics in mathematical neuroscience, including multi-scale networks, neurodegenerative diseases, neural oscillations, and coding. The research presentations were dynamic and well-attended, fostering insightful questions and discussions.

The subgroup remained vibrant despite a modest representation, holding a social gathering on Tuesday evening (July 2) at a local Korean Restaurant. Approximately 15 members attended, enjoying the opportunity to reconnect with old friends and make new connections.

Immunobiology and Infection Subgroup

Immunobiology and Infection Subgroup dinner at KSMB-SMB 2024 in Seoul, South Korea

The Immunobiology and Infection Subgroup hosted a dinner attended by 30 of its members on the Tuesday of the KSMB-SMB2024 conference. Yongdam Jeong helped coordinate a booking for a local Korean BBQ restaurant called HANAM PIG restaurant. The food was delicious and cooked by the staff on BBQs at every table. There was lots of networking and the overarching feedback from the event was that it was really wonderful to spend time as a group. A huge thank you to Yongdam Jeong and Adrianne Jenner who organized and hosted the event. Looking forward to getting together at SMB 2025!

The subgroup’s annual business meeting will be held on September 13, 2024.

Royal Society Publishing

The Royal Society's journals Proceedings A and Interface welcome submissions of research and review articles in Mathematical Biology. They offer a range of services including rapid publication, rigorous peer review, international recognition and the option of open access publication. All Royal Society journals are compliant with funder mandates (such as Plan S). Royal Society Publishing is committed to high quality, open and ethical publishing and, as a not-for-profit society publisher, the income they generate goes back into supporting and progressing the global scientific community by funding the activities of the Society.

Browse recent content from Interface and Proceedings A including GIS-ODE: linking dynamic population models with GIS to predict pathogen vector abundance across a country under climate change scenarios A J Worton, R A Norman, L Gilbert and R B Porter FREELY available!

Browse recent theme issues from Philosophical Transactions A including The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence compiled and edited by Professor Sir Mark Walport and the articles are also FREE to access.

People Section

By Thomas Woolley

Interview with Olivia Chu (Bryn Mawr College), one of our new newsletter editors.

Editorial

After a productive summer - About the SMB and ECMTB Conferences

Reflection on ECMTB

By Burcu Gürbüz

This summer was enriched by two important mathematical biology conferences. First, the joint annual meeting of the Korean Society for Mathematical Biology and the Society for Mathematical Biology (KSMB-SMB 2024 Seoul) was held from June 30 to July 5 at the Konkuk University, Seoul, Republic of Korea. Second, the 13th European Conference on Mathematical and Theoretical Biology (ECMTB'24 Toledo) was held between July 22 - 26 at the University of Castilla La Mancha, Toledo Campus, Spain.

ECMTB'24 was successfully organized by Víctor Manuel Pérez García and his team. The biennial conference brought together leading researchers and academics in Mathematical Biology to discuss current and interdisciplinary topics in applied mathematics, theoretical biology, and also to facilitate the development of new techniques and methodologies for modeling complex biological systems. The conference was attended by more than 5000 participants from all over the world. ECMTB'24 had a rich scientific program with mini-symposium and contributed talks, with poster sessions and also with plenary talks with the following details: Evrim Acar Ataman (SIMULA), Christina Cobbold (University of Glasgow), Patricia Reynaud-Bouret (Université Côte d'Azur), Ivana Bozic (University of Washington), Ganna Rozhnova (University Medical Center Utrecht), Mustafa Khammash (ETH Zurich), Anna Marciniak-Czochra (Heidelberg University). As in previous editions, ECMTB'24 provided a platform for sharing research, fostering collaboration, and sparking new ideas for the esteemed researchers, scholars, and enthusiasts who joined the event in this intellectual endeavor. Alan D. Rendall and I had the privilege of organizing a mini-symposium on mathematical analysis, dynamical systems, mathematical modeling, and numerical perspectives. I was amazed by the hospitality and thoughtful organization of the conference team in the fairytale city of Toledo. In my personal experience, I really enjoyed ECMTB'24 - Toledo as it was great to meet old and new friends and distinguished researchers in the field at this prestigious conference. During the event, the annual meeting of the ESTMB was held and Benoit Perthame gave an informative presentation on the activities of the society. For the motivation of young researchers, poster awards were presented.

In addition to the scientifically rich program, the conference also featured a very thoughtful social program that included a guided tour of the city of Toledo, a cocktail party at the Patio de Covarrubias and a conference dinner at El Cigarral on the Tagus River with a magnificent view of the historic city of Toledo.

Group picture of the ECMTB’24, Patio de Covarrubias, Toledo, Spain

Reflection on KSMB-SMB 2024

By Ryan Murphy, University of Melbourne

The recent KSMB-SMB 2024 conference at Konkuk University, Seoul, Republic of Korea brought together leading and emerging researchers from across the world. The week comprised of a host of fantastic plenaries, mini-symposia presentations, contributed talks and posters, and workshops on the latest advances in mathematical biology across all SMB subgroup areas. It was great to hear the stimulating discussions continue long into the breaks and beyond.

There are too many scientific highlights that it would be unfair to name only a few. Alongside the fantastic science and discussion, the conference will long be remembered for the conference dinner with traditional dancing, Taekwondo/K-POP hybrid followed by a performance of Gangnam Style, the organised excursions, and thoughtful touches. I would also like to thank the conference co-chairs Prof. Yangjin Kim and Prof. Ilhyo Jung, all members of the organising committee and scientific committee, and all helpers for making the event such a brilliant success and for setting such a high bar for future editions.

On a more personal note, as this was my first in-person SMB conference it was fantastic to put faces to names and be welcomed into the community with friendly and engaging discussions. I would also like to thank the SMB for their support in facilitating my participation through the Landahl Travel Grant.

I look forward to seeing you all at SMB 2025!

BMB Article Highlight: Albert C. Soewongsono & Michael J. Landis. (2024)

Wed, 04 Sep 2024 15:54:17 GMT

A Diffusion-Based Approach for Simulating Forward-in-Time State-Dependent Speciation and Extinction Dynamics

by Albert C. Soewongsono & Michael J. Landis

Although diffusion approximations are widely used in population genetics, they remain underused for modelling phylogenetic diversification dynamics. We bridge this gap by establishing a general diffusion-based framework to study a wide and highly influential class of phylogenetics birth-death models, known as cladogenetic state-dependent-speciation-extinction (ClaSSE) models. We validate our diffusion-based framework is reliable under a variety of diversification scenarios. We also derive relationships between model rates and their stationary state frequencies. In summary, our work helps to formalize relationships between evolutionary state patterns, process rates, and mixing times for ClaSSE-type models.

(Upper panel) Relationships between different evolutionary scenarios with species richness at present; (Lower panel) Illustration of an event-based phylogenetic tree viewed as a diffusion-based frequency simulation.

BMB Article Highlight: Chenghang Li, et al. (2024)

Wed, 28 Aug 2024 15:03:48 GMT

Mathematical modeling of tumor immune interactions: the role of anti-FGFR and anti-PD-1 in the combination therapy

by Chenghang Li, Zonghang Ren, Guiyu Yang, Jinzhi Lei

Bladder cancer is a malignant tumors of the urinary system known for its high incidence and recurrence rates. Recent studies suggest that combination therapy could improve survival outcomes for bladder cancer patients with high FGFR and PD-L1 expression. This study introduces a mathematical model that integrates the inter-regulatory network of the tumor microenvironment and the competition mechanism between the drug and the ligand-binding receptor. This model describes tumor proliferation dynamics under various treatment strategies and visualizes these process through an agent-based model. The study analyzes the tumor microenvironment dynamics, combination therapy efficacy, treatment sequencing, disease progression, and patient survival.

The protocol of data-driven mathematical model development and application.

BMB Article Highlight: Brock D. Sherlock et al. (2024)

Wed, 21 Aug 2024 15:29:54 GMT

The Distance Between: An Algorithmic Approach to Comparing Stochastic Models to Time-Series Data

by Brock D. Sherlock, Marko A.A. Boon, Maria Vlasiou, Adelle C.F. Coster

Experimental data is often in the form of time-series data with multiple measurements taken at a number of time points. In biological datasets the number of measurements at each time point is often small. So, it can be useful to consider data from multiple experimental protocols to constrain model parameters. In this study, we identify distance metrics for the comparison of stochastic model outputs and time-evolving stochastic measurements of a system. Our distance is across three scales: that of the data at each time point of each type of experiment; a combined distance across the time course of each experiment; and a combined distance across all the experiments. The distances identified offer a means to fit a wide range of models to data.

The algorithm to produce a hierarchical distance measure over three scales: individual time points, across a time course of a single experiment, and a combined distance over all experiments. This combined distance can then be used for parameter inference, model or other comparisons.

BMB Article Highlight: A. Baabdulla and T. Hillen. (2024)

Wed, 14 Aug 2024 09:56:22 GMT

Oscillations in a Spatial Oncolytic Virus Model

by A. Baabdulla and T. Hillen

A viral infection of the tumor has two effects, the virus infects cells which subsequently lyse to release more virus particles, and, the virus marks cancer cells as infected and the immune system comes in to eradicate them. Both processes have to work in balance as to efficiently clear the entire tumor. The basic model for oncolytic viruses is an SIV predator-prey model, which has a Hopf bifurcation and periodic solutions. An interesting question is the spatial coupling of these oscillators as many different types of spatio-temporal patterns are possible (see Figure). The key question for clinical applications is how to manipulate the virus such that the system is in the oscillatory state. We discuss several of these approaches.

Simulation of an oncolytic virus model using Andrew Krause’s VisualPDE. C shows the cancer cells (brown is low, black is high), I the infected cancer cells (blue is low and white is high), and V the virus (blue is low and red is high).

BMB Article Highlight: Mahasa et al. (2024)

Wed, 07 Aug 2024 05:58:45 GMT

A Role of Effector CD8+ T Cells Against Circulating Tumor Cells Cloaked with Platelets: Insights from a Mathematical Model

by Khaphetsi Joseph Mahasa, Rachid Ouifki, Lisette de Pillis, Amina Eladdadi

Circulation of tumor cells, shed from the primary tumor into the blood stream or lymphatic circulation, posits a great threat for patients having metastatic cancers. In this study, we developed a simple mathematical model describing how the primary tumor, CTCs arrested within the circulation, activated platelets and effector CD8+ T cells all shape metastatic framework. Our simulations reveal that high number of activated platelets on CTCs exacerbate CTC’s evasion from immune surveillance. Our model suggests that the efficacy of immunotherapy, based on CD8+ T cells, can be improved by increasing the proliferation rate of CD8+ T cells, although this resolution should be weighted against the CD8+ T cell toxicity in the circulation.

A schematic diagram of the cellular interactions at the primary site, within the circulation and the secondary site.

BMB Article Highlight: Soloviova et al. (2024)

Wed, 31 Jul 2024 06:59:20 GMT

A mathematical model for fibrous dysplasia: The role of the flow of mutant cells

by Mariia Soloviova, Juan C. Beltrán-Vargas, Luis Fernandez de Castro, Juan Belmonte-Beitia, Víctor M. Pérez-García, Magdalena Caballero

Fibrous dysplasia (FD) is a rare mosaic, non-inheritable genetic disorder that affects the skeleton, where normal bone is replaced by weaker, fibrous tissue. This disorder is characterized by expansible lesions prone to fracture, deformity, and pain, and currently has no cure. We have developed a simple mathematical model to better understand the behavior of bone cells in FD. Our model includes the basic biological processes known to occur in FD and tracks the changes in different populations of bone cells over time. We conducted a detailed analysis of the model, examining its properties, the existence and stability of steady states, and the sensitivity of various parameters.

Representation of the bone-cell populations and interactions between them.

BMB Article Highlight: Surasinghe et al. (2024)

Tue, 23 Jul 2024 06:10:08 GMT

Evolutionary invasion analysis of modern epidemics highlights the context-dependence of virulence evolution

by Sudam Surasinghe, Ketty Kabengele, Paul E. Turner, C. Brandon Ogbunugafor

Why do some pathogens evolve to make their hosts more sick, and others less? This characteristic is embodied in the concept of “virulence,” a central idea in infectious diseases that describes the harm that a pathogen inflicts upon a host. Examining how virulence evolves constitutes a subfield of evolutionary theory, that attempts to make concrete predictions for how we should expect infectious diseases to evolve. In this study, we construct models of various epidemics, and apply a set of mathematical methods based on game theory that identify characteristics of mutant pathogens that render them uninvadable (that is, they cannot be invaded and replaced by a different strain of pathogen). We demonstrate that pathogens that are spread via different routes—“directly” (as in SARS-CoV-2) or “indirectly” as in diseases like hepatitis C virus in a population of persons who inject drugs—have profoundly different expectations for how. Our findings have implications for how we analyze and prevent modern epidemics. We learn that how virulence will evolve is context-dependent. Consequently, our predictive models of the evolution of virulence should be tailor made to fit the particulars of certain infectious diseases.

A diagram of an infectious disease model with multiple evolved strains of a pathogen.

BMB Article Highlight: Fazli, Bertram and Striegel (2024)

Wed, 17 Jul 2024 08:01:33 GMT

Multi-layer Bundling as a New Approach for Determining Multi-scale Correlations Within a High-Dimensional Dataset

by Mehran Fazli, Richard Bertram & Deborah Striegel

The multi-layer bundling (MLB) method delivers a robust new approach to cluster elements of complex biological networks. Using different partitioning schemes (clustering regimes) obtained by spectral clustering on the affinity matrix, MLB provides hierarchical layers of clusters called bundles, where each bundle in a layer is formed from all elements with the same membership throughout all partitioning schemes used up to the current layer. This iterative process offers profound insights into the interconnections among data elements not apparent through a single clustering approach. For example, MLB excels in identifying critical bridge sets within interacting systems. If removed, these bridges can disrupt system compartments and halt information propagation, making their identification crucial for understanding network integrity. Moreover, MLB's unique capability to integrate bundle membership information through multiple layers with the affinity matrix significantly enhances its predictive power in network reconstruction. Compared to methods like WGCNA, MLB offers a more robust and versatile approach. Requiring fewer user-defined parameters, MLB provides a clearer view of the underlying data structures, empowering researchers with a powerful tool to decode complex datasets and uncover meaningful biological insight. Its versatility extends beyond biological networks, making it valuable for various research domains.

BMB Article Highlight: Lacy & Jenner (2024)

Wed, 10 Jul 2024 22:00:20 GMT

Impact of Resistance on Therapeutic Design: A Moran Model of Cancer Growth

by Mason Lacy & Adrianne Jenner

Cancers often develop resistance to standard treatments, such as chemotherapy. Understanding how the appearance of resistant cells impacts the effectiveness of treatment is an important area of study. In this work, we use a Moran model to investigate the impact of resistance on two styles of treatment administration: single high-dose injections (or maximum tolerated dose) and sustained low-dose treatments.

Experimentalists have been developing devices, such as hydrogels, that can be loaded with drug and injected close to the tumour. These devices then release the treatment slowly over time, giving a sustained (often low) dose of the therapy. Using a Moran model capturing a population of sensitive and resistant cells, we were able to show that maximum tolerated dosages are still the most effective protocols in the presence of an aggressive, resistant-prone tumour. We showed how even when the Moran model was calibrated to capture experimental data for treatment of breast cancer, the same result holds.

Caption: Schematic depicting tumour evolution over time and the fixation of a resistant clone following therapy. As a cancer grows, it is subjected to various pressures which can cause mutations to arise. Some clones may contain mutations that may be more adept at coping with treatment or provide a fitness advantage to those cells, such as faster proliferation rates, and we denote these as driver mutations. After treatment, often cells with driver mutations conferring resistance and/or fitness advantages will expand in number. In some cases, this can result in a tumour that is no longer as genetically complex. Most importantly, these tumours are often no-longer sensitive to the original therapy (Color figure online)

Spring 2024 Newsletter

Thu, 27 Jun 2024 21:05:59 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Burcu Gürbüz (Johannes Gutenberg-University Mainz), Thomas Woolley (Cardiff University), and Olivia Chu (Dartmouth College).

News – updates from:
People – New editor Burcu Gürbüz.
Editorial – on Big Moves during academic careers.
Featured Figure – Highlighting the research by early career researcher Veronica Ciocanel, Duke University.

To see the articles in this issue, click the links at the above items.

Contributing Content

If you have any suggestions for content or on how to improve the newsletter, please contact us at any time. We appreciate and welcome feedback and ideas from the community. The editors can be reached at newsletter@smb.org.

We hope you enjoy this issue of the newsletter!

Alys, Sara, Thomas, Burcu, and Olivia

News Section

By Sara Loo and Olivia Chu

SMB Subgroups Update

Cell and Developmental Biology Subgroup

The SMB Cell and Developmental Biology (CDEV) subgroup held its first virtual mini-conference in March 2024 (picture attached), featuring about 25 speakers and panelists, with participants registering from across 5 continents! Our virtual mini-conference “Cell and Development Festival Week” consisted of 5 sessions across 4 days, each with about two hours of programming. Thank you to all who presented and participated. Our subgroup has also continued to post interviews highlighting scientists in mathematical cell and developmental biology. In our three most recent blog posts, we hear from Evan Curcio, Duncan Martinson, and Hannah Scanlon; see https://smb-celldevbio.github.io/blog/ for their interviews, as well as past interviews of other members of the CDEV community.

Immunobiology and Infection Subgroup

As a follow-up to the NIAID/SMB Workshop on Multiscale Modeling of Infectious and Immune-Mediated Diseases held at last summer’s SMB Annual Meeting, the Immunobiology and Infection Subgroup would like to highlight a paper summarizing the event that was recently published in the Bulletin of Mathematical Biology: https://doi.org/10.1007/s11538-024-01276-2 We look forward to organizing similar events/workshops in coordination with other SMB subgroups!

MathOnco Subgroup

Jason George and Harsh Jain’s terms as co-chairs are coming to an end. We are in the process of recruiting 2 co-chairs. Nominations have closed.

The subgroup is also organizing a mini-symposium at the SMB 2024 Annual Meeting in Korea - ‘Emerging Researchers in Mathematical Oncology: The ONCO Group Minisymposium’. This will feature 10 talks by exciting early-career researchers from around the world.

SMB DEI Committee

1. The DEI Committee is pleased to share a recent publication in the Bulletin of Mathematical Biology entitled “Integrating Diversity, Equity, and Inclusion into Preclinical, Clinical, and Public Health Mathematical Models”. The paper is a follow-up from the DEI-focused session and discussion at the 2023 SMB Annual Meeting held in Columbus, Ohio last year. The article presents key issues for the increased integration of DEI in mathematical modelling in biology. Such integration ensures the applicability and relevancy of mathematical models and their predictions to all.

Justin Sheen, Lee Curtin, Stacey Finley, Anna Konstorum, Reginald McGee, and Morgan Craig. “Integrating Diversity, Equity, and Inclusion into Preclinical, Clinical, and Public Health Mathematical Models”. Bull Math Biol 86, 56 (2024). https://doi.org/10.1007/s11538-024-01282-42.

The 2nd Diversity of Math Bio Summer Virtual Seminar Series starts June 4! This series aims to highlight the diversity of mathematical biology research and the diversity of researchers in the field. The talks will be held on Tuesdays at 8:00 PDT / 11:00 EDT / 17:00 CEST via zoom. See the attached flyer for more details and register at https://tinyurl.com/SMB-Diversity-Summer2024 to receive the zoom information. Please join in for an exciting summer of math bio talks!

Dates: June 4, June 18, July 16, July 30, August 30

Confirmed Speakers:
1. June 4: Paola Vera-Licona, University of Connecticut Health Center; Omar Saucedo, Virginia Tech
2. June 18: Punit Gandhi, Virginia Commonwealth University; Maisha Marzan, North Central College
3. July 16: Kristina Wicke, New Jersey Institute of Technology; Celeste Vallejo, Simulations Plus
4. July 30: Van Pham, University of South Florida; Alex Ochoa, Duke University
5. August 13: Malena Español, Arizona State University

Upcoming Conferences and Workshops

Society for Mathematical Biology Annual Meeting

From 30^th June - 5^th July Friday 2024, the joint annual meeting of the Korean Society for Mathematical Biology and the Society for Mathematical Biology will be held at KonKuk University, Seoul, Republic of Korea. For more details check the conference website: https://smb2024.org/

Royal Society Publishing

The Royal Society's journal Proceedings of the Royal Society A welcomes submissions of research and review articles in Mathematical Biology. With a broad, international readership and a thorough, constructive review process, authors can be confident that their work published with us will have an impact.

Browse recent content including articles such as Structural identifiability analysis of linear reaction–advection–diffusion processes in mathematical biology on the website at https://royalsocietypublishing.org/journal/rspa

Proceedings A publishes review articles of interest to a wide range of scientists and the Reviews Editors welcome proposals for new reviews. All review articles are made immediately open access at no cost to the author. See https://royalsocietypublishing.org/rspa/reviews for information on proposing a Review and see some recent review articles at https://royalsocietypublishing.org/toc/rspa/2024/480/2285

People

By Thomas Woolley

We interviewed one of our two new editors Burcu Gürbüz (Johannes Gutenberg-University Mainz). Find out more here.

Editorial

By Alys Clark

Big moves

Moving institutions, or moving countries, is often talked about from the perspective of furthering an academic career. There are benefits from learning a new way of working, or from seeking a career pathway that simply isn’t available at your home institution. Across the field of mathematical biology most of us will have come across students and academics who have moved for one reason or another, and throughout an academic career opportunities may arise to further our careers further afield.

We often discuss the academic considerations around these big moves - are we going to be studying or working at a good institution, what is the reputation of our new supervisor or mentor, and are we going to be moving to a research environment where we are going to be intellectually stimulated and supported? It is really important to talk to those that you will be working with or for, and making sure that the culture of the research team and/or department you will be working for suits you and your background. Perhaps less discussed though are the everyday practicalities of such a move and these may be equally important determinants of success at your new home (be it a short or a long term stay).

I recall on my own (second) international move, for a postdoc position, I found myself in the situation of being unable to open a bank account to pay my salary into without proof of address, and being unable to move into an apartment without proof of finances (i.e. a salary). It is really stressful in your first days or weeks in a new country to be navigating these kind of situations (which are ultimately resolvable) so planning where you might live and the administrative steps you will need to take to set yourself up in advance is desirable. Luckily, there will likely be many that have been in the same situation before you, so your new workplace may be able to put you in touch with people who have recently been through the same process. For those who are moving for employment, working out whether you be eligible for retirement plans (or whether they are transferable if you move again) is also a good idea. Making friends takes time, and joining clubs and community groups can help some to establish networks, but time of life and the community to which you move can influence how long it takes to feel at home. We are all now much more used to online communication which can help you to stay connected with old friends and family. But with patience these connections in your new home build too, so it is worthwhile building those connections even if the move is short term.

There are also international contexts to research priorities and funding. Post-PhD access to research funding may be a priority for establishing a career, but in many countries funding is limited to people with citizenship or residence of the country in question. This may be worth checking before you move to avoid any surprises. In mathematical biology, local priorities may also drive research direction. Will you be able to establish good links to experimental scientists, and are there requirements for ethical approval or consultation specific to your new institution that you should be aware of?

Finally, a move between countries, or even between cities is not for everyone and there are multiple reasons that mean we are best to stay just where we are. Luckily, the thought that we must move to ensure success are fading and there are several opportunities to learn new ways of thinking and doing research from our international colleagues via short term stays or online events. This might include learning from experts in your own field of mathematical biology, or even picking up some experimental skills to complement the theory you are developing. Keep an eye on SMB subgroup news for opportunities, or keep a look out for summer schools or workshops associated with conferences you may be attending online or in person.

Featured Figure

By Sara Loo and Olivia Chu

Early Career Feature - Veronica Ciocanel, Duke University

In this issue, we feature a recent article "Parameter Identifiability in PDE Models of Fluorescence Recovery After Photobleaching", by Veronica Ciocanel, Assistant Professor of Mathematics and Biology at Duke University. We asked Veronica to tell us a bit more about her work here:

Identifying unique parameters for mathematical models describing biological data can be challenging. When studying models of macromolecular dynamics inside cells, spatial movement (characterized by diffusion, transport, and binding dynamics) can be significant and has an impact on the parameters that describe a given model. Therefore, partial differential equations (PDEs) that track the dynamics of proteins as a function of time and space are often an appropriate modeling framework. However, PDEs present challenges when trying to understand identifiability, especially since many established in vivo measurements of protein dynamics average out the spatial information.

In this work, we focus on biological data obtained from a commonly-used and versatile experimental technique for probing protein dynamics in living cells: FRAP (fluorescence recovery after photobleaching). In particular, we would like to understand what insights we can gain from FRAP data about binding protein interactions in RNA localization bodies (biomolecular condensates) in oocytes of the frog Xenopus laevis. We find that known methods of (structural and practical) parameter identifiability have certain limitations for FRAP data and for the reaction-diffusion PDEs describing the binding protein dynamics. We therefore propose a pipeline for assessing parameter identiﬁability and for learning parameter combinations for this model. This method recovers the protein diffusion coefficient in synthetic datasets and predicts and the relationship between binding and unbinding rates in experimental datasets. Ultimately, we would like to use these insights to understand how various protein components interact and bind with RNA in biomolecular condensates.

Figure Caption:

A) Schematic of a stage II Xenopus frog oocyte with RNA granules localizing at the bottom shown in magenta. The black square region is shown magnified on the right, with a cartoon of a FRAP (fluorescence recovery after photobleaching) experimental bleach spot. B) The amount of fluorescence in the bleach spot over time gives rise to the blue experimental FRAP curve (blue). The fit with simulated FRAP data is equally good with two sets of binding/unbinding rate parameters as indicated in panel C). C) Approximation of the likelihood landscape for the non-identifiable parameters.

You can find out more about this research here: https://link.springer.com/article/10.1007/s11538-024-01266-4

BMB Article Highlight: Dixon & Keener (2024)

Thu, 20 Jun 2024 03:26:52 GMT

Dimensional Dependence of Binding Kinetics

by Megan Dixon & James Keener

Experimentally, the strength of protein-protein interactions is typically measured in solution, and dissociation constants are traditionally reported in units of volume concentration. It is often assumed that these three-dimensional dissociation constants give direct insight into how tightly the same proteins bind when they are membrane-associated. In this article, we explore and counter this notion. We demonstrate mathematically that dissociation constants are highly dependent on dimension. In both discrete and continuous space, we present and analyze stochastic models of binding kinetics in one, two, and three dimensions. Not only do dissociation constants in two dimensions have different units and forms than dissociation constants in three dimensions, the conversion between them is quite complex and requires detailed information. We present a novel formula to convert three-dimensional dissociation constants to two-dimensional dissociation constants. This conversion allows for better understanding of protein interactions on membranes and how to appropriately model them.

BMB Article Highlight: Anelone & Clapham (2024)

Thu, 13 Jun 2024 14:19:29 GMT

Measles Infection Dose Responses: Insights from Mathematical Modeling

by Anet Anelone & Hannah Clapham

The measles virus (MV) is highly contagious and affects the whole body, including the skin and the immune system. As MV infection dose increases above one infectious particle, the peak of infectious viral load occurs sooner, yet its magnitude remains constant. It is important to improve understanding of measles, in part due to the re-emergence of measles outbreak worldwide, and a lack of research. We investigated mechanisms determining the outcomes of measles infection doses. We evaluated relevant biological hypotheses, and their respective mathematical formulations, to describe and fit data on the time course of measles infectious viral load in the peripheral blood of monkeys, following experimental measles infection with different doses. When MV infection dose increases, the initial viral load, and the initial number of responding immune cells increase. This mechanism decreases the time it takes for immune cells to control and remove infectious viral load. This mechanism also underpins the dose-independent magnitudes for measles viral load, and the loss of immune cells. Together, these findings suggest that the outcome of measles depends on how the immune system responds to incoming MV right from the beginning. This work encourages prevention, vaccination, and early diagnosis of measles.

Caption: Measles infection dose responses: insights from mathematical modeling. Top: Model-data fits for acute viremia in response to changes in MV infection doses. using model parameterizations and assumptions in Table in the paper. 104, 103, 102, 10 and 1 TCID50 correspond to red diamonds, blue stars, orange triangles, magenta dots, and green squares respectively. The solid lines represent the trajectories generated by the proposed model parameterization. The shapes represent data. The dark grey dotted dashed line represents the limit of detection < 0.3. Bottom: Cartoon illustrating that the healthy body adjusts the response of the immune system to remove measles infectious particles sooner when the measles infection dose increases; however, the peak viral load remains constant

BMB Article Highlight: Suvandjieva et al. (2024)

Thu, 06 Jun 2024 23:47:52 GMT

Modelling the Impact of NETosis During the Initial Stage of Systemic Lupus Erythematosus

by Vladimira Suvandjieva, Ivanka Tsacheva, Marlene Santos, Georgios Kararigas Peter Rashkov

NETosis, or formation of Neutrophil Extracellular Traps (NETs) in response to a pathogenic stimulus, is a suspected contributing factor of autoimmunogenicity in Systemic Lupus Erythematosus. Our ODE-based mathematical model studies the interaction between macrophages, neutrophils and two types of antigen with origin in apoptotic waste and NETs during the initial stage of the disease. Analytical and numerical calculations help classify the bifurcations between equilibria, in particular those with presence of autoantigen. The model predicts that even in parameter regimes with efficient clearance of NETs by immune cells, autoantigen can persist stably in tissue, causing chronic inflammation and loss of immune tolerance in the long run.

Sketch of the interactions between cells and antigens studied by our model.

BMB Article Highlight: Blom & Engblom (2024)

Wed, 22 May 2024 02:48:14 GMT

Morphological Stability for in silico Models of Avascular Tumors

by Erik Blom & Stefan Engblom

We develop a simple, stochastic model of an avascular tumor that displays known behavior at the considered scales. In parallel we develop, analyze, and simulate a surrogate PDE model to explain the growth pattern and shape of the stochastic model.

We investigate the emergent tumor morphology of the stochastic model (Fig. a) through the PDE model and through comparisons of respective model’s numerical experiments. The stochastic model displays the three characteristic avascular tumor regions -- the proliferative rim, quiescent annulus, and necrotic center -- and sigmoidal volumetric growth pattern in line with the PDE model under radial symmetry (Fig. b). The analysis predicts morphological instability under low oxygen and cell-cell adhesion conditions, as well as an ever-present creeping effect where the tumor as a whole migrates towards the oxygen source -- an effect observed during simulations of both models (Fig. c). The analysis further displays a capacity to predict non-trivial morphological patterns of the model tumor (Fig. d).

BMB Article Highlight: Dragicevic (2024)

Tue, 14 May 2024 21:26:04 GMT

The Unification of Evolutionary Dynamics through the Bayesian Decay Factor in a Game on a Graph

by Arnaud Z. Dragicevic

The study unifies evolutionary dynamics on graphs by employing a decaying Bayesian update in the context of strategic uncertainty. It demonstrates that the replication of strategies leading to shifts between competition and cooperation in well-mixed and Bayesian-structured populations is equivalent under certain conditions. Specifically, this equivalence holds when the rate of transition between competitive and cooperative behaviors matches the relative strength of selection pressures. Our findings help pinpoint scenarios where cooperation is favored, independent of payoff levels, expanding the application of Price's equation beyond its original intent.

Caption: The basins of attraction of the Price-wise unstructured population replicator dynamics

BMB Article Highlight: Taylor, Rapaport & Dochain (2024)

Wed, 01 May 2024 21:52:52 GMT

Convex Representation of Metabolic Networks with Michaelis-Menten Kinetics

by Josh Taylor, Alain Rapaport & Denis Dochain

Polyhedral models of metabolic networks are computationally tractable and provide insight into cellular functions. For example, flux balance analysis is a linear program in which reaction fluxes are optimized over polyhedral mass-balance constraints. In this paper, we augment the standard polyhedral model of a metabolic network with a new, second-order cone representation of the Michaelis-Menten kinetics. This enables us to explicitly model metabolite concentrations without losing tractability. We formulate conic flux balance analysis, a second-order cone program in which reaction fluxes are maximized while metabolite concentrations are minimized. While not as tractable as linear programming, second-order cone programs with hundreds of thousands of variables can be solved in seconds to minutes using modern solvers like Gurobi and MOSEK. In addition to predicting both fluxes and concentrations, we can use conic duality to compute sensitivities to kinetic parameters, i.e., maximum reaction rates and Michaelis constants. We also incorporate the second-order cone representation of the Michaelis-Menten kinetics into dynamic flux balance analysis and minimal cut set analysis. These tools provide new, tractable ways to analyze reaction fluxes and metabolite concentrations in metabolic networks. The Python code for each tool is available at https://urldefense.com/v3/__https://github.com/JAT38/conic-metabolic__;!!NVzLfOphnbDXSw!CB8YzXwI0ErdeBFcgljtFA36uhpf2ATRf6MEgYTiLhceaAzDS6gF7M5m047C62AYZH8xjVWlPanu7H7qQcsSzjBGP_RJ4rc$

BMB Article Highlight: Chew & Spill (2024)

Thu, 25 Apr 2024 22:51:35 GMT

Discretised Flux Balance Analysis for Reaction-Diffusion Simulation of Single-Cell Metabolism

by Yin Hoon Chew and Fabian Spill

Metabolism comprises thousands of biochemical reactions. It is commonly modelled using Flux Balance Analysis (FBA), a method based on linear programming, because this method requires very few parameters. However, conventional FBA implicitly assumes that all enzymatic reactions are not diffusion-limited though that may not always be the case.

To enable the exploration of diffusion effects on cellular metabolism, we present a spatial method that implements FBA on a grid-based system. The method discretises a living cell into a two-dimensional grid; creates variables that represent the rates of reactions within grid elements and diffusions between grid elements; and solves the system as a single linear programming problem.

Simulations using the method suggest that factors such as cell shape, diffusion regime and spatial distribution of enzyme can influence the variability and robustness of metabolism at both single-cell and population levels. We propose the use of this method to explore how spatiotemporal organisation of compartments and molecules in cells affect cellular behaviour.

Yin Hoon Chew is a Research Fellow and Fabian Spill is a Professor of Applied Mathematics at the University of Birmingham, UK. Yin Hoon designed and implemented the method, with feedback from Fabian.

The method can simulate living cells with different shapes and heterogeneous enzyme distribution. Simulations suggest that cell shape (perimeter-to-area ratio) does not affect cellular behaviour such as biomass growth when diffusion is fast, but there is a strong effect at low diffusion.

BMB Article Highlight: Twumasi, Cable & Pepelyshev (2024)

Wed, 17 Apr 2024 06:47:53 GMT

Mathematical modelling of parasite dynamics: A stochastic simulation-based approach and parameter estimation via modified sequential-type approximate Bayesian computation

by Clement Twumasi, Joanne Cable and Andrey Pepelyshev.

In an era marked by global health challenges and re-emerging infections, the need for sophisticated and robust mathematical models to better understand infectious diseases has never been more pressing. Our impactful study focused on a biological system known as the gyrodactylid-fish system. While existing modelling studies have fallen short in capturing vital information to reflect the biological realism of this system, our research introduced a novel individual-based stochastic simulation model to realistically simulate the spread of three different strains of Gyrodactylus across three different host populations, enhancing our knowledge of this system given observed experimental data. This study contributed mathematically and biologically to the gyrodactylid-fish system, offering insights that may apply to modelling other biological systems. Expanding on the existing studies, we have added to our understanding of this system and provided answers to open biological questions for the first time through model-based Bayesian analysis. The study also led to robust extensions of likelihood-free Bayesian estimation methods, commonly known as approximate Bayesian computation (ABC), to aid in calibrating complex models with mathematically intractable likelihood. After conducting additional posterior predictive checks, we found our proposed ABC methodologies' efficiency highly compelling and can readily be adapted to fit other highdimensional multi-parameter models.

BMB Article Highlight: Bergman et al. (2024)

Wed, 10 Apr 2024 03:43:36 GMT

Second-Order Effects of Chemotherapy Pharmacodynamics and Pharmacokinetics on Tumor Regression and Cachexia

by Daniel R. Bergman, Kerri-Ann Norton, Harsh Vardhan Jain & Trachette Jackson

This paper presents a novel computational framework that constrains high-dimensional ABM parameter space with multidimensional real-world data. We accomplish this by extending and validating a first-of-its-kind method that leverages explicitly formulated surrogate models to bridge the computational divide between ABMs and experimental data. We show that Surrogate Modeling for Reconstructing Parameter Spaces (SMoRe ParS) can constrain high-dimensional ABM parameter spaces using unidimensional (single time-course) data. We then demonstrate that it can constrain parameter spaces of more complex ABMs using multidimensional data (multiple time courses at different biological scales). To validate our method, we compared the SMoRe ParS-inferred ABM parameter space with ABM parameters inferred by an often computationally expensive direct comparison with experimental data. A strength of SMoRe ParS is that it allows for exploring ABM parameter space even at points that are not directly sampled and where ABM output was never generated. Computationally efficient methods to connect ABMs with multidimensional data are timely and important as ABMs are a natural platform for capturing heterogeneity and predicting emergent behavior in multiscale systems. SMoRe ParS is a robust and scalable computational framework that can explore the uncertainty within multidimensional parameter spaces associated with ABMs representing complex biological phenomena.

Caption: The schematic diagram for using SMoRe ParS to infer ABM input parameters from experimental data via a surrogate model. The solid arrows connecting the Experimental Data and Agent-based Model boxes to the Surrogate Model box represent the direction of information flow in the first few steps of SMoRe ParS. Green (control), yellow (0.75μM oxaliplatin), and red (7.55μM oxaliplatin) colors in the Experimental data box refer to the dosing regimens that generated the experimental data.

Brief description of the roles of the authors (e.g. student, group-leader etc):

Daniel R. Bergman, postdoc

Kerri-Ann Norton, computational modeling collaborator, and developer of SMoRe Pars

Harsh Vardhan Jain, co-senior author and co-developer of SMoRe Pars

Trachette Jackson, co-senior author and co-developer of SMoRe Pars

BMB Article Highlight: Pierik et al. (2024)

Wed, 03 Apr 2024 06:17:19 GMT

Second-Order Effects of Chemotherapy Pharmacodynamics and Pharmacokinetics on Tumor Regression and Cachexia

by Luke Pierik, Patricia McDonald, Alexander R.A. Anderson & Jeffrey West.

Second order effects describe changes in a system which result from introducing variability or fluctuations in a system’s input. Quantifying second-order effects relies on an understanding of the convexity of an underlying function determining system output, and this has been effectively used in several fields, notably financial risk management. Previously, the vocabulary of fragile or antifragile has been used: fragile systems are harmed by variability while antifragile systems benefit from variability. The key insight here is that oncologists can control the input variability of treatment schedules, and therefore it is critical to define the fragility (or antifragility) of tumors. In cancer, second-order effects have been studied through dose response curves, which are ubiquitous theoretical and clinical tools in the field. However, these curves do not incorporate knowledge about how long dosages remain near the tumor (i.e. pharmacokinetics), which influences treatment outcomes. In this paper, we explore this relation between second-order effects and pharmacokinetics through standard mathematical models as well as a previously parameterized tumor model with 5-fluorouracil. By studying second-order effects with pharmacokinetics, more efficient treatment schedules may be devised which utilize the underlying convexity of dose response to produce greater patient outcomes.

BMB Article Highlight: O'Brien & Silcox (2024)

Wed, 27 Mar 2024 01:32:38 GMT

Nonlinear Regression Modelling: A Primer with Applications and Caveats

by Timothy O'Brien & Jack Silcox

In their applied studies, researchers often find that nonlinear regression models are more applicable for modelling various biological, physical, and chemical processes than are linear ones since they tend to fit the data well and since these models – and especially the associated model parameters – are usually more scientifically meaningful. For example in relative potency, drug synergy, and similar compound interaction modelling, key model parameters aid researchers in making important decisions regarding comparisons of drugs or compounds and/or whether combinations of these substances would enhance effects.

These researchers may be at a loss for how best to perform this nonlinear modelling, including choosing between various growth models or binary logistic models, how these work and which analysis methods are best and why. Working through several key examples, this paper provides a gentle yet informative hands-on introduction to nonlinear modelling, provides key R code which can be easily adapted to fit ones own nonlinear models, and underscores key caveats regarding often-problematic Wald confidence intervals and p-values as well as the lack of penalizing for overfitting in a certain large-sample likelihood-based approach.

About the Authors: Tim O’Brien is a professor of Mathematics and Statistics (with a joint appointment in Environmental Sustainability) at Loyola University Chicago. Jack Silcox is a postdoctoral researcher in the Department of Psychology at the University of Utah.

BMB Article Highlight: Browning et al. (2024)

Wed, 20 Mar 2024 06:37:38 GMT

Predicting Radiotherapy Patient Outcomes with Real-Time Clinical Data Using Mathematical Modelling

by Alexander Browning, Thomas Lewin, Ruth Baker, Philip Maini, Eduardo Moros, Jimmy Caudell, Helen Byrne and Heiko Enderling

Mathematical models have the potential to revolutionise clinical practise by providing real-time insights that guide decision-making and predict patient responses. Challenges associated with the application of mathematical models are perhaps, however, most acute for single-patient clinical data of cancer tumour progression. Data are often noisy, sparse, and simplistic; patient responses are often highly variable; and mathematical models may be necessarily complex.

In this work, we develop and present a novel, simple, mathematical model of tumour volume progression in response to radiotherapy that can capture a full gamut of patient responses observed in the clinic. To maximise the utility of data collected from a large clinical cohort whilst accounting for significant patient-to-patient variation, we present alongside the model a Bayesian statistical method that allows for real-time clinical predictions to be drawn throughout a patient's course of treatment.

All model parameters vary between patients, with prior parameter knowledge for new patients informed by a weighted mixture of posterior parameter knowledge from previously observed patients. We demonstrate the ability of our model and statistical framework by considering a subset of patients for which predictions are continuously updated throughout their course of treatment.

The research was led by Alexander Browning (from 2023), a research fellow, and Thomas Lewin (until 2022), a DPhil student.

Caption: Data from a cohort of training data are used to calibrate population-level posterior distributions that account for patient-to-patient variability. Individual-level predictions are then drawn and then updated throughout a patients’ course of treatment

BMB Article Highlight: Dyck et al. (2023)

Adrianne Jenner — Wed, 13 Mar 2024 05:40:39 GMT

Models for implant-induced capsular contracture post breast cancer surgery

by Cheryl Dyck, Kathryn V. Isaac, and Leah Edelstein-Keshet

Surgical breast reconstruction can play an important role in the emotional and psychological outlook of a breast cancer patient. Unfortunately, a common complication of implant-based reconstruction is capsular contracture (CC), formation of a painful and often disfiguring scar-tissue around the implant. Treatment for CC generally requires surgical capsule excision and implant replacement. CC etiology is poorly understood, limiting the ability for determining a patient's risk profile, treatment, and prevention. Here we examine the early stages of CC development with a hierarchy of mathematical models for interacting macrophages, fibroblasts, myofibroblasts, and collagen. A simplified "toy" model provides insight suggesting parameter regimes that lead to either a stable state with a non-pathological thin capsule, a stable state with a pathological thick capsule, and a bistable range in between. A fold bifurcation can exist with the full model with outcome determined by genetic and health profile (parameter values) and inflammatory state (initial conditions.) These results predict some patients are resistant to CC, some are destined to have CC, whereas a susceptible population could develop CC as a result of inflammatory insult. Further examination and clinical study of the parameters of interest may yield risk factors and preventative and therapeutic targets.

Cheryl Dyck MAsc (SFU) is a Mathematical Biology Consultant. Kathryn V. Isaac MD FRCSC MPh, is a Plastic and Reconstructive Surgeon with Vancouver Coastal Health and Providence Health Care, an Assistant Professor, Department of Surgery, Faculty of Medicine, University of British Columbia, Canada and P. Clugston Chair of Breast Reconstruction. Dr. Edelstein-Keshet is a Professor in the Department of Mathematics, University of British Columbia, is the author of "Mathematical Models in Biology (2005) SIAM", and a former president of the Society for Mathematical Biology.

Caption: Schematic diagram for a model of the early phases of tissue recovery around a breast implant (capsule formation.) The implant surgery initiates an immune response that eventually recruits collagen-producing cells. The collagen affects tissue stiffness, and feeds back on the balance between fibroblasts and their activated phenotype, myofibroblasts, further influencing collagen production. Model analysis and simulations predict whether patients are resistant, susceptible, or prone to developing capsular contracture, a painful and disfiguring deformation of the reconstructed breast. Scheme made with Biorender

Winter 2023 SMB Newsletter

Jeffrey West — Fri, 01 Mar 2024 18:58:11 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Fiona R. Macfarlane (University of St Andrews), and Thomas Woolley (Cardiff University).

In Memory: Torcom Chorbajian, Long-time Volunteer and SMB Officer
News – updates from:
People – An interview with Professor Jae Kyoung Kim, who will be a plenary speaker at the Joint Annual Meeting of the Korean Society for Mathematical Biology and Society for Mathematical Biology in Seoul this year.
Editorial – on 'A look forward to KSMB - a chat with Dr Yangjin Kim' on the upcoming SMB-KSMB conference.
Featured Figure – Highlighting the research by early career researcher Ryan Murphy, University of Melbourne.

To see the articles in this issue, click the links at the above items.

Contributing Content

We hope you enjoy this issue of the newsletter!

Alys, Sara, Fiona, and Thomas

In Memory: Torcom Chorbajian: Long-time Volunteer and SMB Officer

Contributed by Lou Gross, Ray Mejia and John Jungck

The Society lost a tremendous long-standing leader and volunteer on January 19, 2024 when Torcom Chorbajian passed away in Lafayette, Colorado. Without any paid staff members, except for those associated with the Bulletin, SMB has functioned over its history due to the dedicated efforts of many volunteers. Torcom was exemplary as the volunteer Treasurer and Board member for nearly forty years. He had tremendous knowledge of the history of the Society and had direct personal connections with the leadership over the first decades, by far attending more Board meetings than anyone else in our history.

As the person who managed membership records, dealt with all financial aspects of the Society and handled interactions with the various publishers of the Bulletin, Torcom devoted untold hours to Society business. He was the one who corresponded with our far-flung membership for decades, handling all kinds of membership and subscription challenges. He took personal interest in our members, particularly those outside North America who relied on their subscriptions to stay informed of the latest research in the time before electronic connections were prevalent. Many were the times he called the current Society President to discuss challenges faced by one of our members and to express concern about sometimes delayed responses from the various publishers. He knew our membership far better than anyone else in the leadership and had attended all of our Annual Meetings for many years. For many meetings, he would manage the display of collections of books to provide our members an opportunity to see the latest texts from various publishers. He handled the distribution of travel funds for many, many students over the years who benefited from the Society’s Landahl awards to enable them to attend meetings (see the photo attached from the 2010 Rio meeting of Torcom writing a check for a student attendee). Torcom also designed the three-sided pens (see photo) handed out at many meetings that are still cherished by members due to the way they sit so comfortably in your hand.

Torcom’s contributions were celebrated in 2008 with the first Torcom Chorbajian Lecture at the Annual Meeting at the University of Toronto. As then-President Gerda de Vries noted in the January 2013 SMB Newsletter “I want to thank Torcom Chorbajian for serving as Treasurer for almost 40 years. Torcom has been a member of the SMB since its inception in the 1970s and was appointed Treasurer two years later. Torcom has accepted the title of Honorary Treasurer of the SMB.” Tocom is remembered as a friend and tireless steward of the SMB and its members.

News Section

By Fiona Macfarlane

SMB Subgroups Update

Cell and Developmental Biology Subgroup

The Cell and Developmental Biology (CDEV) subgroup was active (with minisymposia, contributed talks, posters, a subgroup business meeting, and a group dinner) at the 2023 SMB Annual Meeting in Columbus, OH, and we're looking forward to the 2024 SMB Annual Meeting in Seoul, Korea!

In addition to our activities at the annual meetings and our blog-post series (https://smb-celldevbio.github.io/blog/) highlighting researchers in our community, we started two new virtual initiatives in the last year. First, we held mentored mock virtual interviews for students and postdocs preparing for the academic job market (thanks to all who participated as mentors and mentees!). Second, we are holding our first virtual micro-conference “Virtual Cell and Development Festival Week” from March 18–21, 2024. The schedule features plenary talks on research and professional development topics, several minisymposia, and two panels (focused on industry careers and the future of models and software platforms). Each day of the festival week has about 2 hours of programming, with a range of times selected to fit many timezones. Please see https://smb-celldevbio.github.io/cdevfestival/ for more information and registration details (registration is free). All are welcome and encouraged to attend our first virtual CDEV festival week!

Immunobiology and Infection Subgroup

The Immunobiology and Infection subgroup is excited to host four outstanding speakers in its annual minisymposium at the joint Annual Meeting of the KSMB and SMB, in addition to the many excellent sessions being organized by our members. Join us for talks by Reginald McGee, Wasiur Khuda Bukhsh, Adrianne Jenner, and Past Chair Stanca Ciupe. Hope to see you in Seoul!

At last year’s SMB Annual Meeting at Ohio State University, together with SMB and the National Institute of Allergy and Infectious Diseases (NIAID), our subgroup co-organized a half-day workshop Bridging multiscale modeling and practical clinical applications in infectious diseases. This event brought together top experts in multiscale mathematical modeling with experimentalists and clinicians working at the frontier of immunity and infectious diseases to share their research and discuss challenges and opportunities for future work. We were thrilled to see the high level of interest from conference attendees and are looking forward to organizing a future iteration of the event. If you missed it, or want to relive the fun, the organizing team wrote a summary article which will be forthcoming in the Bulletin of Mathematical Biology, keep an eye out and we will send around when it is published. Thank you to the co-organizers, speakers, and participants.

Mathematical Epidemiology and Mathematical Oncology Subgroups

The Mathematical Epidemiology (MEPI) and Mathematical Oncology (ONCO) subgroups hosted SMB MathEpiOnco 2024, a joint virtual mini-conference February 18-20. Over 150 registered participants from 22 countries attended the three-day meeting. The conference featured plenary talks by Marisa Eisenberg (University of Michigan, USA), Claudia Pio Ferreira (São Paulo State University, Brazil), and Natalia Komarova (U.C. San Diego, USA) as well as a panel discussion of Opportunities at the Interface of Mathematical Epidemiology and Oncology with panelists Hanna Dueck (National Institutes of Health, USA), Zhilan Feng (National Science Foundation and Purdue University, USA), and Ami Radunskaya (Pomona College, USA) and a tutorial session on Stochastic Processes in Epidemiology and Oncology led by Linh Huynh (Dartmouth College, USA) and Pujan Shrestha (Texas A&M, USA). In addition, the conference featured 22 contributed talks for SMB members working on problems in mathematical epidemiology, mathematical oncology, and the intersection of the two fields.

The conference prompted important discussions about similarities in approaches to studying problems in oncology and epidemiology with a mathematical lens and highlighted areas for research growth in questions that are relevant to both fields. Furthermore, the conference underscored important links between infectious disease and cancer that leave open a number of interesting questions that mathematical biologists can explore. The conference closed with a period of discussion in working groups with goals such as Connecting within-host dynamics with population level incidence and transmission dynamics, Investigating the role of models in studying infectious diseases that lead to cancer, and Connecting models and parameters across different types of model structures. Participants in working groups made plans for future projects and mini-symposia to be organized for future scientific meetings.

SMB MathEpiOnco 2024 was organized by Jason George (Texas A&M), Meredith Greer (Bates College, USA), Linh Huynh (Dartmouth College), Harsh Jain (University of Minnesota Duluth, USA), and Michael Robert (Virginia Tech, USA). For more information, visit the conference website:https://seminar.math.vt.edu/SMB-MEPI-ONCO/schedule.html

Upcoming Conferences and Workshops

Society for Mathematical Biology Annual Meeting

From 30^th June - 5^th July Friday 2024, the joint annual meeting of the Korean Society for Mathematical Biology and the Society for Mathematical Biology will be held at KonKuk University, Seoul, Republic of Korea. Early bird registration will be open until 30^th April 2024, for more details check the conference website: https://smb2024.org/

Royal Society Publishing

The following Royal Society theme issue has been highly cited, downloaded and is FREE to access online: ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’ compiled and edited by Dr Jasmina Panovska-Griffiths, Dr William Waites, and Professor Graeme J Ackland - see https://royalsocietypublishing.org/toc/rsta/2022/380/2233

The COVID-19 pandemic has highlighted the importance of mathematical modelling in informing and advising policy decision making. Via a collection of sixteen papers, this issue showcases how the Royal Society coordinated efforts of diverse scientists to help model the coronavirus epidemic and overcome a number of technical challenges. Different papers address the utilisations of different technical modelling frameworks and how different techniques are combined, show how modelling of different scenarios can give informed scientific advice, discuss how to correctly quantify the uncertainty of the model parameters and projections, and flag up the importance of transparency and robustness of models and numerical code to ensure reproducibility of the results. Read more in a blog post by one of the Guest Editors: https://royalsociety.org/blog/2022/08/modelling-epidemics-ramp/

We are also looking for new theme issues and that if you are interested in submitting a proposal, please visit the website https://royalsocietypublishing.org/rsta/guest-editors or contact the Editorial Office for more information - philtransa@royalsociety.org.

People

By Alys Clark

We interviewed Professor Jae Kyoung Kim, Chief Investigator of the Biomedical Mathematics Group at the Institute for Basic Science, Republic of Korea and an academic staff member in Mathematics at the National University in Daejeon, Republic of Korea, find out more here.

Editorial

By Sara Loo

A look forward to KSMB – a chat with Dr Yangjin Kim

As the year continues to tick quickly on and winter comes to an end, we can look forward to many exciting things. Not least of these is the upcoming Korean Society of Mathematical Biology – Society of Mathematical Biology joint meeting in July. In the lead up to this summer’s conference, and as submissions for minisymposia and contributed talks come streaming in, I met with Yangjin Kim, co-chair of the meeting’s organising committee to get to know a bit more about KSMB and what we can expect in Seoul in July.

On a wintery evening over Zoom, we chatted about the history of KSMB. Founded in 2005, its co-founders quickly established bridges across disciplines – one of the founders, Tae-Soo Chon is a biologist. This quickly and firmly founded the society within the biological science community, as well as in its natural habitat in the mathematical sciences. This led to many natural and fruitful collaborations. Starting from very small numbers, the society now draws in over 150 participants at their annual meetings. Beyond this, the society has been a strong advocate for the field in the Asia region, convening the China-India-Japan-Korea Conference on Mathematical and Theoretical Biology last year in Jeju Island, South Korea.

Having been a part of SMB since early in his research career, Yangjin speaks fondly of his experiences at SMB conferences. His passion for creating a similar environment for others across many different regions is evident. “I grew up with SMB”, he mentions. He has only missed two meetings since his first in Raleigh in 2005, and as a PhD student he earned himself a Landahl Travel Grant in 2006. These influences are long-reaching, and throughout our conversation he is reminded of how beneficial the society has been to him – “I always feel comfortable when I attend the SMB meeting every year… having a chance to talk to people in my research area and getting [to meet] mentors.” He has encouraged his students to attend the yearly meetings and “it has been wonderful for them, they say.”

He tells me how fruitful his interactions with SMB members have been. He has worked with many mentors and peers throughout his career and time as an SMB member – his thesis advisor Hans Othmer, Avner Friedman, Mark Chaplain, amongst others. Being a part of a community of like-minded peers and receiving advice, feedback and, even, criticisms from others in the society have marked his career. In some sense, he “[sees] it as the center of [his] career.”

This sort of environment is something he values greatly, and something he seeks to share with researchers all over the world. I ask him what he hopes the conference will be like, or something he hopes it may achieve. “I want it to be really international”, he says. Though Yangjin trained in the US and spent 13 years there in his early career, his position at Konkuk University in South Korea has allowed him to grow and cultivate excitement and interest for the field in Asia. Throughout Asia, other regional societies of mathematical biology have popped up, and are starting to grow – the Phillipine Society for Mathematical Biology was launched earlier this year, and the CIJK conference last year was its eighth iteration. Holding KSMB-SMB in Seoul will be a great foundation for these smaller societies to gain support and interact with members of our larger community, stimulating ongoing research in the region. Already, they have seen a range of diverse abstracts from many Asian countries and young scientists.

So what else can we look forward to in Seoul in July? Yangjin mentions excellent food, beautiful modern and traditional buildings, some K-pop, a beautiful campus and perhaps some drone flying is on the cards. Beyond that, take a moment to be thankful for the joint meeting and the commitment of the organising committee in pulling this off. This was originally planned for 2022 and though it was inevitably postponed, here we are 2 years later. “It is a long time coming, [we] almost got exhausted from asking ‘when are we going to have this!’”, Yangjin laughs. It took many years of preparation, discussions have seen multiple SMB presidents, and ongoing commitment from the SMB board and members of KSMB. 감사합니다 See you in July!

Featured Figure

By Thomas Woolley

Early Career Feature - Ryan Murphy, University of Melbourne

In this issue, we feature the article “Formation and growth of co-culture spheroids: New compartment-based mathematical models and experiments”. This research was performed by Ryan J. Murphy (University of Melbourne), Gency Gunasingh (University of Queensland), Nikolas K. Haass (University of Queensland), and Matthew J. Simpson (Queensland University of Technology).

Tumour spheroid experiments are routinely performed to investigate cancer progression and test anti-cancer therapies. In our previous studies, we have connected the seminal Greenspan mathematical model to monoculture tumour spheroid growth data for the first time, leading to practical experimental design recommendations and quantification of the time evolution of spheroid structure (necrotic core, proliferation-inhibited intermediate region, proliferating rim). By considering time-dependent oxygen conditions, we also revealed that tumour spheroids can experience surprising necrotic core dynamics and transient reversal of growth phases that had been well-characterised for over fifty years.

In this study, we consider co-culture tumour spheroid growth experiments. Co-culture spheroid experiments are challenging to interpret as they are comprised of two or more cell types that may have different characteristics, such as differing proliferation rates or responses to nutrient availability. The dynamics are further complicated by multiple biological processes occurring on overlapping timescales. As Greenspan’s model has been valuable in analysing monoculture spheroid data, we first connect Greenspan’s model to co-culture data for the first time. We find that parameter estimates are consistent for co-culture spheroids seeded with different initial proportions of two cell types. However, since the model assumes all cells behave identically, it cannot capture experimentally observed internal dynamics of growing co-culture spheroids.

For greater insights, we generalise a class of compartment-based mathematical models previously restricted to spheroids composed of one cell type, such as Greenspan’s model, so that they can be applied to spheroids consisting of multiple cell types. It is then straightforward to develop and explore multiple natural two-population extensions to Greenspan’s seminal model, where the populations may differ with respect to their proliferation rate, death rate, response to nutrients, or migration preferences. By connecting these new models to data, we reveal biological mechanisms that can describe the internal dynamics of growing co-culture spheroids and those that cannot. This mathematical and statistical modelling-based framework is well suited to analyse spheroids grown with multiple cell types, and the new class of ordinary differential equation-based mathematical models provide opportunities for further mathematical and biological insights.

You can find out more about this research here: https://link.springer.com/article/10.1007/s11538-023-01229-1

BMB Article Highlight: Murphy et al. (2023)

Adrianne Jenner — Mon, 26 Feb 2024 05:04:42 GMT

Formation and Growth of Co-Culture Tumour Spheroids: New Compartment-Based Mathematical Models and Experiments

by Ryan J. Murphy (University of Melbourne), Gency Gunasingh (Frazer Institute, University of Queensland), Nikolas K. Haass (Frazer Institute, University of Queensland), Matthew J. Simpson (Queensland University of Technology)

Co-culture tumour spheroid experiments are routinely performed to investigate cancer progression and develop anti-cancer therapies. However, they are challenging to interpret as they are composed of two or more cell types that undergo multiple biological processes on overlapping timescales. In this study, we interpret new co-culture spheroid experimental data using Greenspan’s seminal monoculture model and multiple new and natural two-population extensions of Greenspan’s model. This allows us to reveal biological mechanisms that can describe the internal dynamics of growing co-culture spheroids and those that cannot. The mathematical and statistical modelling-based framework is well-suited to analyse spheroids grown with multiple different cell types. Further, the new class of compartment-based mathematical models, which includes Greenspan-type models as a special case, provide opportunities for further mathematical and biological insights.

Dr Ryan J. Murphy performed the mathematical and statistical modelling. Ms Gency Gunasingh performed the experimental work. Professor Nikolas K. Haass and Professor Matthew J. Simpson contributed equally.

BMB Article Highlight: Walker et al. (2023)

Adrianne Jenner — Mon, 19 Feb 2024 08:06:55 GMT

VisualPDE: Rapid Interactive Simulations of Partial Differential Equations

by Benjamin J. Walker, Adam K. Townsend, Alexander K. Chudasama & Andrew L. Krause

Mathematical biology and other areas of science are employing increasingly complex models that take the form of partial differential equations. Such models can exhibit a rich set of behaviours, including those that defy intuition, such as diffusion-driven pattern formation. In this paper we present VisualPDE, a web-based tool enabling real-time interactive exploration of such models. We feel that such interactive 'play' is an incredibly important and under-utilized way to develop intuition and build deep understanding of these models.

The paper opens by saying that a reader should simply go and play on the website, VisualPDE.com, themselves. It then outlines our rationale for developing this tool, some of the technical and design issues we faced, as well as some of the examples and use-cases we have already explored. The structure of this paper supplements the 'living' website with things we think a reader might find interesting, particularly around the wider context and technical aspects of designing the website. We hope it helps the wider community deepen our understanding of PDE models, and rethink how we teach and do research using mathematics more generally.

Image caption: This is an interactive simulation on the website which can also be viewed at https://visualpde.com/sim/?preset=BMB . It uses spatial heterogeneity to force a reaction-diffusion system to exhibit both a complex prepattern and emergent spot-like patterns in different parts of the domain.

BMB Article Highlight: Kravtsova et al. (2023)

Adrianne Jenner — Wed, 31 Jan 2024 06:25:56 GMT

Scalable Gromov-Wasserstein Based Comparison of Biological Time Series

by Natalia Kravtsova, Reginald L McGee and Adriana T Dawes

In this paper, we introduce a rigorous and powerful method for comparing time series data using a novel and computationally efficient modification of the Gromov-Wasserstein optimal transport distance. In brief, our method, which we denote GW$_{\tau}$, views each trajectory as a separate metric space and compares these metric spaces via optimal transport. This feature of our method makes it exceptionally flexible in the types and size of data sets that can be compared, including data sets that occur on different time scales, are missing measurements, or even lie in spaces of different dimensions. Its rigorously demonstrated properties show a clear increase in efficiency and accuracy over other methods and using a variety of data. Using our method, we show that averaging time series using recently proposed Fused Gromov-Wasserstein barycenters provides more reliable average trajectories compared to the most commonly used mean trajectories. Our easily implemented and fast GW$_{\tau}$ method can be applied to a wide range of time series data, from cell biology to ecology, and allows for new comparisons and quantifications that preserve key features in the data sets.

Natalia Kravtsova, a student author, led the research in this paper, including formal analysis, methodology, and visualization. Prof. McGee and Prof. Dawes provided supervision. All three authors contributed to the formulation and conceptualization of the research, and manuscript preparation.

Autumn 2023 Newsletter Part 2

Jeffrey West — Fri, 26 Jan 2024 04:04:10 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Fiona R. Macfarlane (University of St Andrews), and Thomas Woolley (Cardiff University).

People – Interviews with Dr Adrianne Jenner and Dr Michael Watson.
Editorial – on 'Research that is worth a thousand words: Visualising a conference' on the theme of conference illustration.
Featured Figures – Highlighting the research by early career researcher Chloé Colson and highlighting the most accessed paper from the Bulletin of Mathematical Biology August 2023 issue.

People

By Sara Loo

We interviewed Dr Adrianne Jenner, lecturer at Queensland University of Technology, find out more here.

We interviewed Dr Michael Watson, lecturer in Applied Mathematics at the University of New South Wales in Sydney, Australia and co-chair of the Cardiovascular Modelling subgroup, find out more here.

Editorial

By Thomas Wooley

Research that is worth a thousand words: Visualising a conference

Conferences, workshops, and study groups serve as critical hubs for innovative discussions and interdisciplinary collaborations. Yet, the traditional format of these gatherings has remained steadfast – talks, slides and projectors. Unfortunately, the insights shared during these talks often prove to be as transient as a fading dream, slipping away quickly, leaving us with fleeting memories.

Taking notes during lectures can help, and if the speaker is willing, you can supplement them with presentation slides. However, more often than not, we find ourselves returning from these events with notebooks filled with intricate spider diagrams and hastily scribbled ideas that seem more at home on a conspiracy theorist's corkboard.

The most recent innovation has been recorded talks; you can literally relive the presentation. However, spotty connection issues, poor sound recording and non-existent video editing aside, surely, we must be able to make memory recall more… fun?

While lectures and presentations will always be the core of these gatherings, there's an untapped approach that could revolutionise the conference experience – conference illustration. Illustrations are not only visually captivating, making even the most mundane topics intriguing, but they also provide tangible outputs that can be used to showcase current and future work, satisfy funding requirements, and elevate audience engagement.

An illustrated talk by Maria Abou Chakra on the presentation The Climate Game.

My introduction to this practice occurred during the COVID-19 pandemic when Maria Abou Chakra's remarkable work began circulating on Twitter. I wholeheartedly encourage you to explore her talents in mathematical biology and artistry by following her on Twitter, @MariaAbouChakra, (yes, I refuse to call it X) and visiting her collection of sci-sketches on her website (http://individual.utoronto.ca/abouchakra/sci-sketchnotes/). Her work is both beautiful and highly informative. She truly is a renaissance woman with a foot both in the science and the aesthetic!

I've had the privilege of presenting for Maria at the "Modelling Cell Development and Regeneration Discussion Group," and I've consistently used her illustrations to convey my work to academic and lay audiences. They're undeniably more appealing than a slew of equations and technical jargon.

Maria’s illustration of my talk about putting stochasticity, or “noise”, in biological patterning systems.

During a recent conversation with Maria, she explained how illustrating talks helped her retain information, focusing on the core concepts rather than minutiae. She generously shared some valuable tips for those aspiring to follow in her footsteps:
1) Organize your sketch space, decide where elements like titles, conclusions, and key ideas should be placed. Preparation is key, as space can fill up quickly.
2) Technology is not a prerequisite; a pen, pencil, and paper can be a great starting point.
3) If you prefer technology, consider using software like Autodesk SketchBook (free) or Procreate.
4) Familiarize yourself with the features and brushes of your chosen app.
5) Practice. Skills are honed over time through effort and dedication.

However, for those without the time, skills, or inclination for such artistry, consider hiring an illustrator for your next conference. It's important to acknowledge that while these artists may not come cheap, their work holds immense value. In an era where AI produces "art", we must not underestimate the genuine skill of condensing and presenting information in a visually curated manner. We should be willing to compensate those with artistic talents, ensuring that such skills don't become lost, or devalued, in the face of automation.

If you're working with a tight conference budget, I understand that this may not be your top priority. However, if you have some flexibility in your finances, take a moment to explore the pool of talented illustrators available. You may be pleasantly surprised by the options at your disposal. Posting a message on Twitter, or Facebook could yield enthusiastic responses from skilled illustrators.

In a recent conference on interdisciplinary IVF challenges, https://thefertilitynetwork.wixsite.com/infer, conducted with my colleague Dr Katerina Kaouri and funded by GW4, https://gw4.ac.uk/, we were fortunate to have some extra funds available. After evaluating our options, we decided to engage a local artist, Eleanor Beer (https://www.eleanorbeer.com/), as our conference illustrator.

Eleanor readily admitted she wasn't an IVF expert, but this was precisely the point. She focused on capturing the big ideas and overarching themes of the conference, not on mining details for her next research paper.

Eleanor Beer’s illustration of our recent “Interdisciplinary Challenges in IVF” conference.

Unsurprisingly, both the delegates and the organizing committee were thrilled with Eleanor's work. She provided us with a piece of art that we eagerly anticipate displaying in our department. It stands as a constant reminder of our funding success and the continuing scientific challenges that need to be addressed.

As we uncover the potential of incorporating illustrators into conferences, it becomes clear that their contributions have the power to revolutionize how we disseminate and absorb information. Their work transcends language barriers and kindles our scientific creativity. The benefits are substantial, and it is high time to recognize and embrace the visualization of conferences.

Featured Figures

By Fiona Macfarlane

Early Career Feature - Chloé Colson, University of Oxford, UK

In this issue, we highlight research from Chloé Colson, a PhD student at the University of Oxford (UK) working with Philip Maini and Helen Byrne. We asked Chloé to tell us a little more about their paper `Investigating the Influence of Growth Arrest Mechanisms on Tumour Responses to Radiotherapy’:

Cancer is a heterogeneous disease, with tumours of the same type exhibiting large variation at the genotypic and phenotypic levels. These differences can have a significant influence on tumour sensitivity to treatment and, more generally, on patient prognosis. Improving our understanding of the mechanisms underpinning cancer is, therefore, essential for the development of effective patient-specific therapeutic protocols. In this paper, we aim to assess how two distinct mechanisms of growth control may affect tumour responses to radiotherapy (RT), an established cancer treatment used to treat more than 50% of cancer patients.

In previous work (Colson et al. 2022), we developed a novel ordinary differential equation model of solid tumour growth which distinguishes between growth arrest due to nutrient insufficiency, when cell proliferation and death rates balance, and due to contact inhibition, when the cell proliferation rate converges to zero, with no cell death. While it has been shown that both of these mechanisms can be simultaneously active in vitro in 2D monolayer and 3D spheroid assays (Helmlinger et al. 1997), most models of tumour growth only describe a single growth control mechanism. By considering both nutrient and space limited growth, our model exhibits three distinct regimes: nutrient limited (NL), space limited (SL) and bistable (BS), where both mechanisms of growth arrest coexist.

In the present work, we extend our tumour growth model to include time-dependent responses to RT and systematically study RT response in the three growth regimes introduced above. We construct three virtual populations of NL, SL and BS tumours, and, for each population, we initially consider tumour responses to a conventional fractionation schedule consisting of 5x2 Gy fractions per week for 8 weeks. We determine average responses and explore how values of key parameters (i.e., the tumour oxygen consumption rates (q₁, q₃) and the vascular volume) generate extreme (i.e., strongly positive and negative) behaviour. We find that tumour responses to RT are regime-dependent, with tumours in the SL cohort responding positively and tumours in the BS cohort responding poorly. We also identify the biological processes that may explain positive and negative treatment outcomes in each regime. For instance, as shown in the Figure, we find that increased RT efficacy for SL tumours may be due to limited tumour regrowth and/or RT cell kill. Finally, by studying the impact of the total dose and dosing frequency on tumour response, we elucidate how dosing strategies that maximise the reduction in tumour burden vary between regimes; higher doses applied at higher frequency are beneficial for SL tumours, whereas lower doses applied at lower frequency can be more effective for NL and BS tumours.

Subject to the validation of our findings with experimental data, we believe that our modelling framework has the potential to help guide patient-specific treatment protocol design and, thus, contribute to improving patient prognosis.

You can find out more about this interesting work here: https://link.springer.com/article/10.1007/s11538-023-01171-2

Most accessed article in the Bulletin of Mathematical Biology in August 2023

The article entitled “Could Mathematics be the Key to Unlocking the Mysteries of Multiple Sclerosis?” was the most accessed article in the August edition of the Bulletin of Mathematical Biology. This article was written by Georgia Weatherley, Robyn P. Araujo, Samantha J. Dando and Adrianne L. Jenner from the Queensland University of Technology.

In this paper, the authors review the existing mathematical efforts to understand multiple sclerosis (MS), a neuroimmunology disease affecting the brain and spine. The goal with this review was to highlight the opportunities for mathematicians to have major impact on MS, both in terms of diagnosis, prognosis and improving treatment design.

MS is a neurodegenerative disease where myelin, which surrounds and protects neurons in the brain and spine, is degraded by an overactive immune system. The loss of myelin causes a range of physical and cognitive impairments for which there is currently no cure. Existing mathematical models of MS, while limited in volume in comparison to diseases such as leukemia or malaria, are diverse and insightful. Modelling works range from non-spatial deterministic models (ODEs) to spatially deterministic models (PDEs) and spatially stochastic models (ABMs).

The authors summarise, to the best of their knowledge, all existing mathematical efforts to capture MS across the four major disease scales: population, systemic, CNS and molecular (cellular). As such, this review serves as a foundation for future modelling works in MS.

The modelling techniques developed by mathematical oncologists and immunologists are readily translatable to MS and could provide much needed answers to open problems in this complex, profoundly heterogeneous disease. This review is a call to arms for the mathematical biology community, complete with a list of open problems that could benefit from a mathematical approach.

You can find out more about this interesting work here: https://link.springer.com/article/10.1007/s11538-023-01181-0

https://ahurford.github.io/aarms-summer-school/index.html

Autumn 2023 Newsletter Part 1

Jeffrey West — Fri, 26 Jan 2024 04:01:28 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Fiona R. Macfarlane (University of St Andrews), and Thomas Woolley (Cardiff University).

News – updates from:
- SMB Subgroups
- Past Conferences and Workshops

To see the articles in this issue, click the links at the above items.

Contributing Content

We have an upcoming newsletter editor position available, please get in touch if you would like more information on what is involved.

We hope you enjoy this issue of the newsletter!

Alys, Sara, Fiona, and Thomas
Editors, SMB Newsletter

News Section

By Alys Clark

SMB Subgroups Update

Mathematical Epidemiolgy (EPI) and Mathematical Oncology Group (ONCO)

The Mathematical Epidemiology and Mathematical Oncology subgroups are partnering to host a virtual mini-conference February 18-20 (12-4 p.m. EST/UTC-5). The mini-conference will include three plenary talks, contributed talks, a panel on opportunities at the intersection of mathematical epidemiology and oncology, and more! It will emphasize research advances at the intersection of mathematical oncology and infectious disease modeling. Registration and Abstract Submissions will open in December. For more details, join the MEPI and/or ONCO subgroups or contact MichaelRobert@vt.edu. The organizing committee includes: Jason George (Texas A&M), Meredith Greer (Bates College), Linh Huynh (Dartmouth), Harsh Jain (University of Minnesota-Duluth), and Michael Robert (Virginia Tech).

Mathematical Oncology Group (ONCO)

We are pleased to announce that the ONCO subgroup will be organizing a minisymposium at the upcoming SMB meeting in Korea. This event will showcase the work of promising early-career researchers who are making exciting and significant contributions to mathematical oncology.

Thank you for your continued support, and we look forward to your participation in our upcoming events! Please also consider volunteering to serve as the next co-chair of our subgroup. The ONCO subgroup is co-chaired by Jason George (term ends in 2024), Linh Huynh (term ends in 2025), and Harsh Jain (term ends in 2024).

Mathematical Neuroscience Group

The Mathematical Neuroscience subgroup is pleased to introduce its new officers for the 2023-2025 term, as follows:

Chairperson: Yangyang Wang (Brandeis University, US, yangyangwang@brandeis.edu)

Vice-Chair: Chitaranjan Mahapatra (Paris Saclay University, France, c.mahapatra97@gmail.com)

Advisory Members: Hammed Fatoyinbo (Massey University, New Zealand, hammed@aims.edu.gh), Cheng Ly (Virginia Commonwealth University, US, cly@vcu.edu)

Conferences and Workshops

Reporting from the Atlantic Association for Research in the Mathematical Sciences and the Emerging Infectious Diseases Modelling (AARMS-EIDM) Summer School (19-31 Aug Newfoundland, Canada)

Submitted by Francisca Olajide

The Atlantic Association for Research in the Mathematical Sciences and the Emerging Infectious Diseases Modelling (AARMS-EIDM) Summer School, organized by Dr. Amy Hurford (Memorial University of Newfoundland and Labrador) took place at Bonne Bay Marine Station, in Norris Point on the breath-taking west coast of Newfoundland, Canada between August 19 and August 31, 2023. The summer school gave 39 participants the unique opportunity to enrol in two well-structured graduate-level mathematics courses, ”Mathematical Epidemiology" and “Data, Models, and Decision Support", both taught by seasoned professors, in a highly collaborative learning environment.

Commencing the sessions, Dr. Amy Greer (University of Guelph) delivered an enlightening lecture on “Simple Epidemiological Models". As a young enthusiast in infectious disease modelling, I found the teaching explicit enough for anyone aiming to connect the domains of mathematics and epidemiology. In her lecture on “Host Heterogeneity", Dr. Greer highlighted heterogeneity in disease transmission and used the concept of the “WAIFW (Who-Acquires-Infection-From-Whom)" matrix to have participants see how incorporating heterogeneity in models helps to better understand disease dynamics and to estimate quantities such as age-dependent forces of infection.

During one of her sessions, Dr. Jane Heffernan (York University) presented a seemingly straightforward, yet thought-stimulating question: “Why make models?" Dr. Heffernan connected Fibonacci numbers, animal coats, and fractals to the notion of understanding patterns in the world around us. This connection highlighted an underlying rationale for making models. She further taught on in-host models, multi-pathogen models, and evolution, high-lighting how these kind of models can help us to better understand complexities in disease dynamics.

Dr. James Watmough (University of New Brunswick) took us further from models to forecasting. Dr. Watmough stated that forecasting is a scientific method; using the logistic growth equation, he demonstrated how to incorporate probabilistic components to quantify uncertainties in process and observation. Furthermore, he underscored the necessity of associating any valuable prediction with an assessment of its accuracy and reliability. In the context of infectious disease modelling, participants gained insight into addressing diverse sources of uncertainty that could arise from modelling disease dynamics, parameter selection, and making predictions.

Continuing from there, Dr. Amy Hurford delved into characterizing uncertainties. Dr. Hurford demonstrated the techniques for sensitivity analysis and uncertainty analysis, including Latin Hypercube Sampling and Monte Carlo simulations. She also covered the topic of “Decision Support", emphasizing the significant role of modelling in estimating the potential outcomes of decisions through relevant case studies.

Dr. Julien Arino gave an introduction to “Stochastic epidemiological models", illustrating why stochasticity matters by making a distinction between what the basic reproduction number conveys, in both deterministic and stochastic contexts. Dr. Arino demonstrated how to use the Gillespie algorithm to simulate Continous-time Markov chains (CTMC), a commonly used stochastic system. Additionally, he provided insights into the spatio-temporal spread of diseases, highlighting mobility as a key driver, using case studies of the Black Death and SARS-CoV-1.

The Summer School also featured talks from guest lecturers. Dr. Bouchra Nasri (One Health Modelling Network for Emerging Infections, Université de Montreal) discussed the vision for building a One Health data portal, based on a data source, documentation, and modelling approach to foster collaboration among researchers, public health agencies, and other relevant stakeholders. Dr. Steve Walker (McMaster University) discussed the Interna- tional Infectious Disease Data Archive, which integrates historical and publicly available incidence, mortality, and population data. Dr. Brenda Wilson (Memorial University of Newfoundland and Labrador) discussed decision-making in healthcare from both clinical and policy perspectives. In her words, “Not making a decision is an action", while stating that it is important to understand how to manage uncertainty and urgency. Dr. Edward Thommes (Sano Pasteur, University of Guelph) took us through the process of building ensemble forecasts by combining individual forecasts, using a case study of seasonal influenza forecasts in Ontario.

The course content was extensive, and the instructors also did an excellent job integrating making models, handling uncertainties, and decision-making. They were very comfortable with questions from participants, which made the learning atmosphere even more warm and conducive for further discussions on class materials or research interests. Indeed, the summer school was an intensive 12 days of learning epidemiological concepts, advanced mathematical techniques, statistical methods, and computational skills, needed to holistically tackle infectious disease concerns.

Participants also had the opportunity to effectively apply tools and techniques learned in the summer school courses to collaboratively work on innovative projects aimed at advancing infectious disease modelling. This is particularly significant due to the diverse academic backgrounds of the participants, enabling them to cross-pollinate ideas, combine interdisciplinary insights, and effectively address infectious disease questions. Ultimately, this experience has better equipped participants with the skills and tools needed for infectious disease modelling to support decision-making in public health.

On the side, participants had the chance to explore some of the attractions in and around Norris point. While some participants hiked the 7:7 km out-and-back Tablelands trail, others did the 11.7 km Tablelands off-trail loop. The hike was a highlight of the summer school, as it allowed participants to bond and experience the geological diversity of the Tablelands trail. Some of the participants explored the Bonne Bay Marine Station Aquarium while the more adventurous ones went on the Western Brook Pond Tour. “The summer school was definitely a unique and enjoyable experience," remarked Qiuyi Su, a postdoctoral researcher from York University.

In an interview with CBC Newfoundland Morning, Dr. Amy Hurford stated that the choice of having the summer school at Bonne Bay Marine Station was to bring together and equip the next round of young infectious disease modelling researchers in an environment that allows for connection, collaboration, innovation, and community building. Indeed, from having dinner together to working on group projects and sharing research interests, participants built strong connections among themselves. “The summer school did not only teach us how to build models to solve infectious disease problems, but also how to connect, collaborate, and build relationships", wrote George Adu-Boahen, a Master's student from Memorial University of Newfoundland and Labrador, in his feedback.

Being a part of the summer school was an unforgettable experience, and we would like to express gratitude to all who made it possible. The summer school was supported by the Atlantic Association for Research in the Math ematical Sciences (AARMS), Mathematics for Public Health, the Canadian Network for Modelling Infectious Diseases, the One Health Modelling Network for Emerging Infections, Memorial University, and the Canadian Centre for Disease Modelling. A big thank you to Dr. Amy Hurford for organizing such an incredible event.

Further information about the summer school can be found here:

Reporting from the Workshop on Mathematical Perspectives on Immunobiology (11-14 Sept, Blagoevgrad, Bulgaria)

Submitted by Peter Rashkov (IMI-BAS)

The workshop was organized by the Institute of Mathematics and Informatics (Bulgarian Academy of Sciences) and was hosted by the South-West University’s Conference Centre Bachinovo in Blagoevgrad. The scientific programme included plenary talks, oral presentations, a poster session, and round-table discussion. The forum had a great turnout with 25 on-site and 4 online participants hailing from Algeria, Bulgaria, Cameroon, Canada, Czech Republic, Denmark, France, Germany, Great Britain, Hungary, Israel, Spain, and the United States. Nearly a third of the participants were PhD students or young researchers.

The plenary talks covered a wide range of scientific topics: overview of recent findings on virus evolution, systems pharmacology for optimized anticancer therapies, neutrophil dynamics in cancers, antiviral treatment for Sars-Cov-2, immunotherapy in cancer, and the role of inhibitory killer-cell immunoglobulin-like receptors in modulating T cell dynamics. This diversity reflects the wide applicability of mathematical models and methods in immunobiology. The round-table discussion focused on current problems in higher education in mathematical biology. Among the points raised were: fragmentation of research between mathematics, biology and computer science, general decline of interest in mathematics among high-school and university students, but also increased awareness of the importance of scientific and mathematical research during the Covid-19 pandemic among policymakers and the general public.

The Workshop’s organisers acknowledge the generous support from a SMB International Grant that enabled the participation of four PhD students at the workshop, and thank the Conference Centre’s staff for their hospitality. The gentle weather in Blagoevgrad and the pleasant atmosphere of the mountain forest and peaks in the background rounded off the event.

For more information, access the website: http://www.math.bas.bg/nummeth/workshop2023/

BMB Article Highlight Erban and Kang (2023)

Adrianne Jenner — Tue, 16 Jan 2024 22:43:34 GMT

Chemical Systems with Limit Cycles

by Radek Erban and Hye-Won Kang

Hilbert's 16th problem asks questions about the number of limit cycles that a planar polynomial system of ODEs can have. The solutions of such ODEs are two functions of time, x(t) and y(t), which can be plotted in the x-y plane as shown in the picture for an example which has four stable limit cycles, plotted using the black dashed lines as the four closed curves (periodic solutions). Other solutions of the same ODEs (plotted using different colours) all approach one of the limit cycles.

This example has been constructed using the approach developed in the paper, where we investigate limit cycles in chemical systems. Chemical systems with N=2 chemical species can be described by planar ODE systems. A lower bound on the maximum number of stable limit cycles in such chemical systems has been proven in the paper. This directly implies a lower bound on Hilbert's number H(n) denoting the maximum number of limit cycles for general planar n-degree polynomial ODE systems. In the paper, we also study more general systems with N>2 chemical species. We construct chemical systems with K stable limit cycles, where K can be arbitrarily large.

About the authors:

Radek Erban is a Professor of Mathematics at University of Oxford. Hye-Won Kang is an Associate Professor at University of Maryland.

BMB Article Highlight: Brush and Lewis (2023)

Adrianne Jenner — Wed, 03 Jan 2024 00:27:09 GMT

Coupling Mountain Pine Beetle and Forest Population Dynamics Predicts Transient Outbreaks that are Likely to Increase in Number with Climate Change

by Micah Brush and Mark A. Lewis

Mountain pine beetle (MPB) have spread well beyond their historical range, with destructive consequences for forests in Canada. We here present and analyze a new model that couples forest growth to MPB population dynamics to address long term questions about the risk of further spread and inform management strategies, particularly under climate change. This model captures key aspects of MPB biology, including a threshold for the number of beetles needed to overcome tree defenses and beetle aggregation that facilitates mass attacks. These mechanisms lead to a demographic Allee effect, which is known to be important in beetle population dynamics. We show that as forest resilience decreases, a fold bifurcation emerges and there is a stable fixed point with a non-zero MPB population. We derive conditions for the existence of this equilibrium. We then simulate biologically relevant scenarios and show that the beetle population approaches this equilibrium with transient boom and bust cycles with period related to the time of forest recovery. As forest resilience decreases, the Allee threshold also decreases. Thus, if host resilience decreases under climate change, for example under increased stress from drought, then the lower Allee threshold makes transient outbreaks more likely to occur in the future.

Image caption:

A graphical representation of the model dynamics. Pine beetles infest trees by mass attack, overcoming host defenses. They overwinter under the bark of the tree before emerging and dispersing the following summer. This is connected to a forest growth model where saplings grow everywhere there is available light before becoming susceptible to pine beetle attack. After they are infested, they die. Tree needles turn red the year following infestation, and are lost the following year, clearing room on the forest floor for new growth.

BMB Article Highlight: Weatherley et al. (2023)

Adrianne Jenner — Thu, 21 Dec 2023 01:09:45 GMT

Could mathematics be the key to unlocking the mysteries of multiple sclerosis

by Georgia Weatherley, Robyn P Araujo, Samantha J Dando & Adrianne L Jenner

Our review of the existing mathematical models of multiple sclerosis (MS) is designed to highlight the opportunities for mathematics to unlock the mysteries of this disease. Rising in prevalence, MS is an autoimmune, neurodegenerative disease that results in the demyelination of nerve axons and causes physical and cognitive impairment. Existing mathematics models of MS, while limited in volume in comparison to diseases such as cancer and malaria, are diverse and insightful. They range from non-spatial and spatial deterministic models to agent-based models and other stochastic modelling techniques. So far, these models have successfully furthered our understanding of T cell responses, the underlying oscillatory dynamics of the disease, and potential treatment avenues. For mathematical oncologists and immunologists, MS presents a rich and rewarding opportunity to use transferable modelling techniques to shed light on this complex, profoundly heterogeneous disease. This review is a call to arms for the mathematical biology community, complete with a list of open problems that could benefit from a mathematical approach.

Georgia Weatherley is a PhD candidate at Queensland University of Technology, supervised by Adrianne Jenner and Robyn Araujo. This review was written and conceived in collaboration with Samantha Dando. All authors contributed to the writing and editing.

BMB Article Highlight: Colson et al. (2023)

Adrianne Jenner — Thu, 14 Dec 2023 01:01:14 GMT

Investigating the influence of growth arrest mechanisms on tumour responses to radiotherapy

by Chole Colson, Philip K Maini & Helen M Byrne

In this paper, we investigate how nutrient and space limited mechanisms of growth control impact tumour responses to radiotherapy (RT). By distinguishing three growth regimes: nutrient limited (NL), space limited (SL) and bistable (BS), where both mechanisms of growth arrest are active, our study reveals qualitative differences between the RT responses of tumours in the monostable (i.e., NL and SL) regimes and the BS regime. In particular, NL and SL tumours have largely positive responses to treatment, while RT is deleterious for tumours in the BS regime. We find that the positive and negative responses observed in the monostable and BS regimes, respectively, may be underpinned by different biological mechanisms. Further, the RT dosing strategies that maximise the reduction in tumour burden also vary between regimes; higher doses applied at higher frequencies are beneficial for SL tumours, whereas lower doses applied at lower frequencies can prove more effective for NL and BS tumours. Subject to validating our findings against experimental data, we believe that our modelling framework may help guide patient-specific treatment protocol design and, thus, contribute to improving patient prognosis.

Chloé Colson is a PhD student, Philip K. Maini is a Professor of Mathematical Biology and director of the Wolfson Centre for Mathematical Biology, and Helen M. Byrne is a Professor of Mathematical Biology.

Summer 2023 Newsletter

Jeffrey West — Thu, 07 Sep 2023 20:46:42 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Fiona R. Macfarlane (University of St Andrews), and Thomas Woolley (Cardiff University).

News – updates from:
People – Interviews with Prof. Ivana Bozic, the 2023 recipient of the Akira Okubo Prize, and Dr Chengyue Wu, recipient of the 2023 H.D. Landahl Mathematical Biophysics Award.
Editorial – We have included an overview of the SMB 2023 meeting in Ohio, from the SMB subgroups.
Featured Figures – Highlighting the research by early career researchers Elijah Counterman and Sean Lawley, and highlighting the most downloaded paper from the Bulletin of Mathematical Biology June 2023 issue.

To see the articles in this issue, click the links at the above items.

Contributing Content

We have an upcoming newsletter editor position available, please get in touch if you would like more information on what is involved.

We hope you enjoy this issue of the newsletter!

Alys, Sara, Fiona, and Thomas

Editors, SMB Newsletter

News Section

By Thomas Woolley and Sara Loo

SMB Subgroups Update

Cardiovascular Modeling

The Cardiovascular Modeling subgroup would like to officially welcome its new advisory committee members Jessica Crawshaw (University of Oxford), Mitchel Colebank (UC Irvine) and Seth Weinberg (Ohio State University). Thanks to Jessica, Mitchel and Seth for helping to organise and coordinate the subgroup activities at SMB 2023!

Mathematical Epidemiology

Michael Robert (Assistant Professor, Virginia Tech) has taken over as chair with new subgroup co-chair Meredith Greer (Professor, Bates College). Michael and Meredith are looking forward to working together this year to continue the momentum built by Lauren over the past year to lead an active and engaged MEPI subgroup.

Michael Robert is an assistant professor of mathematics and faculty affiliate of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP) at Virginia Tech. He received his B.S. in mathematics from Mississippi State University and his PhD in Biomathematics at North Carolina State University. His research focuses on developing mathematical models to study the evolutionary, ecological, environmental, and anthropogenic processes underlying the emergence, spread, and control of vector-borne diseases. His current projects include modeling the role of climate in the ongoing emergence of dengue in Central Argentina, studying the relationships between climate and dengue spread throughout the Dominican Republic, investigating the effects of infection-altered bioamine levels on Anopheles mosquito behavior and transmission of malaria, and developing mathematical models to study how inequities may arise in the control of mosquito-borne diseases in economically heterogeneous populations. In addition to his work with the MEPI subgroup, Michael is a current co-chair of the SMB membership committee.

Meredith Greer is a Professor of Mathematics at Bates College. She has served as chair of the Mathematics Department, of the Natural Sciences and Mathematics Division, and of the Digital and Computational Studies Program (though not all at the same time!). She earned her BA in mathematics from the University of Delaware and her MS and PhD in mathematics from Vanderbilt University, with a PhD thesis focusing on prion proliferation. Since then, her projects have included the spread of H1N1 influenza and mumps on college campuses; conspiracy theory modeling; oscillation in historical smallpox data; effects of Gloeotrichia echinulata on lake eutrophication; dynamics of softball pitching; collaborations between mathematics and other courses (including rhetoric and biology) for student engagement and new understandings; and a course on precalculus-level mathematics topics motivated by scientific applications. Her current project is the development of an Open Educational Resources text on mathematical epidemiology for undergraduates.

People

By Fiona Macfarlane

We interviewed Prof. Ivana Bozic, the 2023 recipient of the Akira Okubo Prize, find out more here.

We interviewed Dr Chengyue Wu, recipient of the 2023 H.D. Landahl Mathematical Biophysics Award, find out more here.

Editorial

By Sara Loo and the SMB subgroups

An overview of the SMB 2023 meeting from the SMB subgroups

The Society’s subgroups are a key way in which members meet and interact within focused interest groups. Some of these subgroups have been established for many years, while others are just growing. They are hubs to not only bond over shared research interests and the sharing of scientific ideas, but to keep in touch, socialize and develop ongoing friendships and collaboration. Though many subgroups meet throughout the year, post to their own blogs, and send out their own newsletters, it is during the annual meeting that the value of these subgroups really shines through – not just through gathering over pizza or Mexican food, but through organizing minisymposia.

To highlight these efforts, we reached out to our subgroup committees to hear more about what they got up to during the recent SMB meeting in Ohio. These, and the rest of our SMB subgroups, can be found at the SMB subgroup page – reach out to their committee members to hear more and be added to their list of members.

Immunology and Infection:

The IMMU section had a great turnout at the 2023 annual meeting. 7 mini symposia and 3 contributed sessions covered topics ranging from viral and immune system dynamics, agent-based models, model fitting, parameter estimation, eco-evolutionary models, and more. SARS-COV-2 featured heavily this year but presentations on a dazzling diversity of systems included B cells, T cells, transplantation, Tuberculosis, Alzheimer’s Disease, HIV antibiotic resistance, Usutu virus, Equine Infectious Anemia virus, biofilms, CAR-T cells, neutrophils and more. A particular highlight was the special joint session with NIAID which featured fantastic talks and a panel from worldwide experts on modeling, data science, and collaborations between modelers and experimentalists. We hope to include more sessions like this in the future to continue to foster connection and exciting interdisciplinary science/mentorship. A big thank you to everyone who helped judge abstracts and posters!

Mathematical Neuroscience:

The SMB Mathematical Neuroscience subgroup was active at the 2023 SMB annual meeting at Ohio State University. In addition to posters and several contributed talk sessions, there were a number of mini-symposia that spanned a range of topics, including: multi-scale networks, ophthalmology, neural oscillations, dynamics, and coding. The research talks were very lively and well-attended, with very good questions and answers. The subgroup was active despite the modest representation, holding a business meeting and a social outing. One of the highlights was a social gathering on Tuesday evening (July 18) at a Mexican Restaurant. About 20 members attended, catching up with old friends and making new ones. With insights from the subgroup business meeting held during the annual meeting, we are in the process of carrying out electronic elections to determine new subgroup officers for the 2023-2025 term.

Cell and Developmental Biology:

The Cell and Developmental Biology (CDEV) Subgroup had a great time at the SMB Annual Meeting in Columbus. Our subgroup mini-symposia featured topics including data-driven modeling and topological techniques in cell and developmental biology, polarity and patterns in biochemical dynamics, stochastic effects in cell biology across scales, connections between models of pattern formation and experimental results, the role of the microenvironment in controlling cell phenotype decisions, computational models in developmental and cell biology (honoring the work of Prof. Ching-Shan Chou), and cellular biomechanics and fluid dynamics. We announced upcoming CDEV talks on our Twitter account during the conference through @SMBdevBio.

We held a CDEV business meeting during the annual meeting (and followed it with pizza at Adriatico’s, across the street from Jennings Hall). We highlighted our ongoing activities during this meeting and got great feedback on what our subgroup members would like to see from CDEV in the coming year. We’ve continued featuring interviews with scientists through our monthly blog—check out https://smb-celldevbio.github.io/blog/ to learn more. Our two most recent interviews highlight Dr. Robyn Shuttleworth from Altos Labs and Dr. Sasha Shirman from Applied BioMath. CDEV also continues to encourage folks to join the biweekly discussion group “Modeling cell development and regeneration” run by Dr. Maria Abou Chakra (more info at: https://smb-celldevbio.github.io/initiatives/). Based on the feedback that we received during the CDEV business meeting, we’re looking forward to planning a mini virtual conference on cell and developmental biology in the future, and we’re brainstorming offering mock interviews to help prepare early-career researchers for postdoc and faculty jobs.

We are grateful to the volunteers who judged CDEV posters, to the CDEV presenters and minisymposium organizers, to the participants at our CDEV business meeting, and especially to the Ohio State organizing team!

Cardiovascular Modeling:

The Cardiovascular Modelling subgroup was excited to host its inaugural mini-symposium at the SMB 2023 Annual Meeting. Consistent with the subgroup’s overall vision, the session “Integrating Mathematics Across the Cardiovascular System: A Mini-Symposium on Multilevel Modelling of Cardiovascular Biology” brought together researchers using a variety of mathematical and computational techniques to study problems across all levels of the cardiovascular system. Highlights of the session (pictured) included talks on multiscale computational modelling of hemodynamics in pulmonary hypertension (Mette Olufsen, North Carolina State University), dual lipid-structured and phenotype-structured modelling of atherosclerotic plaque formation (Keith Chambers, University of Oxford), and two-dimensional modelling of intracellular calcium dynamics in the sinoatrial node (Nicolae Moise, Ohio State University). Thanks to all the speakers for an exceptional session of talks!

DEI:

The SMB DEI Committee hosted a DEI Plenary session on mathematical modeling and the integration of diverse and underserved populations in (pre) clinical research and public health at the SMB Annual Meeting in Columbus, Ohio. Thank you to those who attended the talks by Dr. Maureiq Ojwang and Justin Sheen, and the Q&A panel that followed, consisting of the speakers as well as Dr. Renee Brady-Nicholls.

The Committee also facilitated a Diversity Lunch during the Annual Meeting. Thank you to the many SMB members who opted to sit at the DEI lunch tables and engage in meaningful conversations! If you did not have a chance to do so during the lunch (or even if you did not attend the meeting), we encourage you to check out the attached poster or slides for information about the DEI Committee's initiatives in the past years.

The DEI Committee welcomes your feedback, suggestions, and participation at this Google form: https://forms.gle/fMtPCcEQfYxsA17SA.

Mathematical Oncology:

MathOnco featured 6 minisymposia with a total of 40 talks and 34 poster presentations. Research projects reflected the exciting work occurring across many topics in mathematical oncology, including evolutionary game theory in cancer progression, dynamics of cellular heterogeneity, and state-of-the-art techniques and methods in modeling cancer treatment. We also thank Renee Brady-Nicholls for serving as a co-chair over the past 2 years, and we welcome Linh Huynh as the new incoming co-chair!

Mathematical Epidemiology:

The Mathematical Epidemiology (MEPI) subgroup was well-represented at the 2023 SMB Annual meeting with six distinct mini-symposia across 8 sessions, 4 contributed sessions, and 21 posters. Several of the MEPI mini-symposia were the product of working groups formed during the MPEI-PDEE mini-conference in February 2023 and highlighted work relevant to both subgroups. Across all talks and posters, a greater diversity of diseases when compared to recent years were represented, including malaria, dengue, COVID-19, Lyme disease, West Nile virus, avian influenza, foot-and-mouth disease, and Rift Valley fever. The role of mathematics in studying the important relationships between climate, the environment, and infectious diseases was explored in talks in the mini-symposia “Zoonotic Infectious Disease Models” and “Climate and vector-borne disease: insights from mathematical modeling,” and the importance of scale in epidemiological models was discussed in the eight talks that were part of the “Disease Dynamics Across Scales” mini-symposium. Methods for improving infectious disease models were explored in a set of two mini-symposia, including “Recent advances in parameter identifiability of mathematical models in mathematical biology” and “Integrating Data with Epidemic Models: Challenges and Opportunities.” The MEPI subgroup leadership organized one mini-symposium, “Mathematical Epidemiology: Infectious disease modeling across time, space, and scale,” and this mini-symposium highlighted the diversity of research within the MEPI subgroup as well as the diversity of researchers from numerous underrepresented groups across multiple career stages.

During the annual meeting, members of the MEPI subgroup gathered at a local brewery in Columbus to enjoy an evening of catching up after multiple years of primarily virtual interactions. This is the first social gathering of the MEPI subgroup since before 2020, and we hope to continue this tradition at all future SMB annual meetings. The MEPI subgroup would like to extend its gratitude to Lauren Childs (Associate Professor, Virginia Tech) who served as chair of the subgroup from September 2022-July 2023. Among the many accomplishments during her tenure, Lauren originated monthly news updates, led the efforts to organize and host the 2023 MEPI-PDEE mini-conference, and organized an excellent MEPI mini-symposium for the SMB 2023 Annual Meeting.

Thanks to all SMB subgroups for their ongoing commitment to engaging in our community.

Featured Figures

By Alys Clark

Early Career Feature - Elijah Counterman and Sean Lawley, University of Utah

In this issue, we feature Lee A Segal prize for best student paper winner Elijah Counterman, who along with Sean Lawley wrote the paper entitled “Designing drug regimens that mitigate nonadherence”. Both are at University of Utah. Here Elijah and Sean tell us more about this exciting research:

What should you do if you miss a dose of medication? Skip the missed dose and take the next scheduled dose as normal? Take an extra dose to make up for the missed dose? These questions sparked our recent work on stochastic modeling of medication nonadherence.

Medication adherence refers to the extent to which patients take medications as prescribed by their physicians. Medication nonadherence is an age-old problem, as even Hippocrates warned physicians to “keep watch also on the fault of patients which makes them lie about the taking of things prescribed.” Today in the United States, it is estimated that medication nonadherence accounts for up to 25% of hospitalizations, 50% of treatment failures, and around 125,000 deaths per year. Remarkably, the World Health Organization has claimed that improving adherence may have a far greater impact on public health than any improvement in specific medical treatments.

There are at least three major hurdles which hinder the study of medication nonadherence. First, clinical trials which force patients to miss doses of the medication being tested could be unethical. Second, nonadherence is by nature erratic, as patients do not miss doses in precise patterns. Third, there are many parameters (adherence rates, drug absorption and elimination rates, dosing intervals, etc.) to vary in any systematic investigation, and it is difficult to disentangle the individual contributions of each of these parameters. For all of these reasons, mathematical modeling and stochastic analysis is an important tool for studying and mitigating nonadherence.

The aim of our work was to use mathematical modeling to design drug regimens to mitigate deleterious effects of nonadherence. Based on our mathematical results, we proposed principles for drug regimens that are robust to nonadherence. In particular, we (i) showed the benefit of taking a double dose following a missed dose (i.e. an extra “make up dose”) if the drug absorption or elimination rate is slow compared to the dosing interval and (ii) quantified the resilience of extended release drugs to nonadherence.

Mathematically, our model took the form of the standard single compartment pharmacokinetic model with first order absorption and elimination, except that the drug intake was a stochastic process modeling the erratic missed doses of the patient (see Figure). We then used stochastic analysis to study the resulting random drug level in the body (see Figure). This mathematical analysis required generalizing a class of random variables known as infinite Bernoulli convolutions whose rather exotic probability distributions have been studied in the pure mathematics literature for many years, dating back to Paul Erdos and others in the 1930s.

You can find out more about this work here: https://link.springer.com/article/10.1007/s11538-021-00976-3

Most downloaded article in Bulletin of Mathematical Biology in June 2023

The article entitled “Forecasting Pathogen Dynamics with Bayesian Model-Averaging: Application to Xylella fastidiosa” was the most downloaded article in the June edition of the Bulletin of Mathematical Biology. This article was written by Candy Abboud, Eric Parent, Olivier Bonnefon and Samuel Soubeyrand (INRAE, France’s National Research Institute for Agriculture, Food and the Environment, Candy Abboud is now with American University of the Middle East, Kuwait). The paper addresses a Bayesian model-averaging approach to the important problem of pathogen dynamics as they enter into new territories – and the problem of predicting future pathogen invasion based on past behaviours informed by past data.

The study used spatially mapped data acquired over four years showing the presence of the Xylella fastidiosa (Xf) bacterium in Corsica (France), which has the potential to put endemic, patrimonial and ornamental plant populations at risk, as well as certain food growing industries. The data is complemented by maps of winter temperature which would impact the spread of the pathogen, but in an unknown manner. Alongside this unknown are the impacts of the location at which Xf was introduced to the region, and the timing of its introduction. A group of mechanistic candidate partial differential equation (PDE) models was used to describe Xf dynamics in the region, and the paper explored 27 scenarios: three representing the nature of growth and diffusion of Xf (homogeneous diffusion and heterogeneous growth, heterogeneous growth and diffusion, and heterogeneous diffusion and homogeneous growth), alongside 9 temperature thresholds which define a reduction in the capacity for Xf to propagate/reproduce. A Bayesian model-averaging approach was used to predict approximately two years of infection from a training set of the prior two year’s data, using the candidate PDE models. The figure shows the training data, alongside out-of-sample predictions for the testing data, the results of a number of different in-sample predictors calculated from the training data. Overall, the Bayesian model-averaging approach provided the lowest root mean square error against the training data, with a relatively large uncertainty in inference, which certainly better represents the possible variability in the future dynamics of the Xf distribution than the uncertainty generated by the other competing predictors.

You can read more about this interesting work here: https://link.springer.com/article/10.1007/s11538-023-01169-w

tinyurl.com/SMB-Diversity-Summer2023

Spring 2023 Newsletter

Fri, 31 Mar 2023 07:40:30 GMT

Alys Clark (University of Auckland), Sara Loo (Johns Hopkins University), Fiona R. Macfarlane (University of St Andrews), and Thomas Woolley (Cardiff University).

News – updates from:
People – Interview with Prof. Trachette Jackson, recipient of the Leah Edelstein-Keshet Prize.
Editorial – Guest editorial from the SMB DEI committee highlighting the DEI panels from ECMTB 2022.
Featured Figures – Highlighting the research by early career researcher, Sara Hamis (Tampere University) and highlighting the most downloaded paper from the Bulletin of Mathematical Biology in February 2023.

To see the articles in this issue, click the links at the above items.

Contributing Content

We welcome your submissions to expand the content of the newsletter. The next issue will be released in late August, so if you would like to contribute, please send an email to the editors by the start of August 2023 to discuss how your content can be included. This could include summaries of relevant conferences that you have attended, suggestions for interviews, professional development opportunities etc. Please note that job advertisements should be sent to the SMB digest rather than to the newsletter.

We hope you enjoy this issue of the newsletter!

Alys, Sara, Fiona, and Thomas
Editors, SMB Newsletter

News Section

By Sara Loo

In this issue of the News section, we highlight the updates from the SMB Subgroups, Royal Society Publishing and the upcoming SMB Conference. Read on below.

SMB Subgroups Update

Mathematical Epidemiology Subgroup & Population Dynamics, Ecology and Evolution Subgroup

The Mathematical Epidemiology (MEPI) subgroup in collaboration with the Population Dynamics, Ecology and Evolution (PDEE) subgroup ran a joint virtual mini-conference in late February. The conference ran from 12-4 pm (EST) across three days to allow more than 200 registered participants from many areas around the world to attend. The schedule featured plenary talks by Folashade Agusto (University of Kansas), Benito Chen-Charpentier (University of Texas, Arlington) and Brandon Ogbunu (Yale University) as well as 18 contributed talks from researchers working on a range of topics in epidemiology, ecology and evolution. In addition to the stimulating talks, the conference featured a panel discussion on funding and research at the interface of Mathematical Epidemiology, Ecology and Evolution with Luis Fernando Chaves (Indiana University, Bloomington) and Zhilan Feng (Purdue University and NSF).

To round out the conference, participants broke into working groups on a variety of topics, some of which resulted in upcoming mini-symposium at the SMB Annual Meeting. The MEPI subgroup leadership, Lauren Childs (Virginia Tech) and Michael Robert (Virginia Tech) give many thanks to the co-organizers from MEPI and PDEE Christina Cobbold (University of Glasgow), Daniel Cooney (University of Pennsylvania), Gilberto Gonzalez-Parra (New Mexico Institute of Mining and Technology), Annalisa Iurio (University of Vienna), Rocio Caja Riveria (University of South Florida) and James Watamough (University of New Brunswick) without which the mini-conference could not have run.
Conference website: intranet.math.vt.edu/SMBEpiPDEE/

Immunobiology and Infection Subgroup

The Immunobiology and Infection subgroup, the Society for Mathematical Biology (SMB), and the National Institute of Allergy and Infectious Diseases (NIAID) are organizing a half-day workshop on Bridging multiscale modeling and practical clinical applications in infectious diseases. The workshop will take place during the 2023 SMB meeting at Ohio State on July 18th from 1pm-5pm EST with a networking event to follow. Registration for the workshop can be done when registering for the Annual Meeting. Information on the schedule and speakers is available on the workshop’s website. Hope to see you there!

Mathematical Neuroscience Subgroup

The Mathematical Neuroscience subgroup is in dire need for fresh new people with new ideas to consider running for subgroup officer positions, all of the current officers’ terms are finished in July 2023. For those in the Mathematical Neuroscience community who want to be a part of SMB, we urge you to consider running for a subgroup officer position. Our subgroup in particular has many established organizations / conferences (Society for Neuroscience, Computational Systems Neuroscience (COSYNE), NeurIPS, Organization for Computational Neuroscience (OCNS), SIAM, etc.) that make it challenging to recruit new and effective officers, but there are exciting possibilities to grow MathNeuro within the broader Mathematical Biology community via SMB.

We currently have 3 to 5 officer positions filled, including: Chair, Vice-Chair, Advisory Committee Members (at least 1 and up to 3). After serving for 4 years, Cheng Ly is looking to step down as chairperson if we can find someone else, and the Vice-Chair (Pam Pyzza) will definitely end her role after July 2023. The other member (Advisory Committee, Chitaranjan Mahapatra) will also be up for re-election.

Royal Society Publishing

JOURNAL OF THE ROYAL SOCIETY INTERFACE

The following Royal Society issues have been highly cited, downloaded and are also fully OPEN ACCESS:

Technical challenges of modelling real-life epidemics and examples of overcoming these compiled and edited by Dr Jasmina Panovska-Griffiths, Dr William Waites, and Professor Graeme J Ackland and the articles are FREELY available online at www.bit.ly/TransA-2233 Read more in a blog post by one of the Guest Editors.

Modelling that shaped the early COVID-19 pandemic response in the UK

Compiled and edited by Ellen Brooks-Pollock, Leon Danon, Thibaut Jombart and Lorenzo Pellis and the articles are FREELY available online at www.bit.ly/PTB1829. A print version is also available at the special price of £40.00 per issue from sales@royalsociety.org.

Royal Society Publishing are also looking for new theme issues and if you are interested in submitting, please visit the website royalsocietypublishing.org/rsta/guest-editors or contact the Editorial Office for more information – philtransa@royalsociety.org.

Upcoming Conferences and Workshops

Diversity in Math Bio Summer Seminar Series

Join the Society for Mathematical Biology and the DEI Committee as we celebrate diversity in mathematical biology this summer! Learn about the breadth of research in math bio and hear from diverse mathematical biologists! Seminars will be via Zoom at 11:00 EDT / 17:00 CEST bi-weekly on Tuesdays. Register to receive the Zoom information:

Workshop on Mathematical Perspectives on Immunobiology

September 11-14 in Blagoevgrad, Bulgaria. Topics include mathematical modeling and computational analysis of phenomena and processes in the immune system, host-pathogen interactions, onset, and progress in human diseases. See the webpage for more details: www.math.bas.bg/nummeth/workshop2023/

Viral dynamics workshop

July 4-6 in Nagoya Japan. A smaller meeting focused intensely on modeling virus dynamics. See the webpage for more details: iblab.bio.nagoya-u.ac.jp/special/2023/virus

People

By Alys Clark

This issue’s interview is with Professor Trachette Jackson. Full interview here.

Editorial

SMB DEI Panels highlighted unique career paths and inclusive graduate programs at ECMTB 2022

By Anna Konstorum and Jess Kreger, on behalf of the SMB DEI committee

The highly interdisciplinary nature of mathematical biology means that in all stages of a professional career, researchers and educators will be faced with challenges ranging from how to structure equitable graduate programs, to how to build meaningful career paths in the field. In the spirit of addressing these challenges, the SMB’s Diversity, Equity, and Inclusion (DEI) committee organized two enriching panel discussions at ECMTB 2022 that allowed panelists to share their personal and professional experiences and advice.

The first panel, Equity of Paths into Mathematical Biology, was hosted live by Adam MacLean (USC), co-hosted and co-organized by Stacey Finley (USC) and Anna Konstorum (Yale U.), and featured speakers Miranda Lynch (Hauptman-Woodward), Luis Sordo Vieira (U. Florida), and Aurélie Carlier (Maastricht University). The panelists discussed how their unique backgrounds contributed to their perspectives and experiences in mathematical biology. With backgrounds ranging from pure math (Sordo Vieira) to biomedical engineering (Carlier) and statistics (Lynch), the panelists provided advice on what sort of resources researchers should seek out regardless of their background, including seeking out mentors and collaborators who can help fill in background that may be missing, taking advantage of professional societies to expand one’s network, and learning how to communicate with non-mathematicians. There was a strong consensus that it was necessary to build meaningful dialogue and collaborations with biologists, and to work to educate them on what is needed for effective model development. Sordo Vieira reminded listeners to not self-disqualify themselves from goals that may seem like a pivot from their background. Good advice for those engaged in interdisciplinary research!

The second panel, Building inclusive graduate programs in mathematical biology, also hosted live by MacLean and co-hosted and co-organized by Veronica Ciocanel (Duke U), Daniel Cruz (U. Florida), and Jesse Kreger (USC) featured Suzanne Sindi (UC Merced), Alun Lloyd (NCSU), Gibin Powathil (Swansea U), and Padmini Rangamani (UCSD). Each of the panelists discussed their experiences building inclusive graduate programs where program requirements are focused on student success and students are supported in their coursework/research. There was great discussion on topics ranging from changing archaic program “standards” to graduate student compensation and housing issues. Common themes throughout included 1) while inclusive recruitment strategies have recently been a hot topic for many programs, the focus for program leaders needs to also be on retainment and support for current students, and 2) that recruitment, retainment, and building inclusive programs requires a large amount of both emotional and physical labor – and that the duty to do the hard work falls on all faculty in positions of power. The panel concluded with a critical student-focused question: “What advice to give to a student who is not feeling valued or supported in their program?”, with Sindi encouraging students to “Find. Your. People.” and Rangamani reminding us to “define value for yourself. Value does not come from [your] CV.”

The SMB DEI committee acknowledges limitations of the panels hosted; there is always more to do. In particular, the panels at ECMTB had a US-centered focus, especially with regards to teaching and PhD mentorship. We hope future discussions will draw in more geographical diversity of our international society. Overall, we have taken away from these panels reminders that may help others, regardless of career stage: reminding us of the importance of collaboration, of networking, and of respect, for ourselves and for those around us. We look forward to continuing the conversation.

At the SMB 2023 annual meeting, the SMB DEI committee will host a new DEI Session and Panel, as well as a lunch gathering for SMB members interested in learning more about the committee and providing input. All SMB members are invited to continue and join these important conversations in person. For more details on DEI and all events at the SMB 2023 annual meeting, visit 2023.smb.org/.