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The National Science Foundation (NSF) has awarded Associate Professor of Mathematics Hwayeon Ryu and Assistant Professor of Biology Efra Rivera-Serrano a three-year, $500,138 grant to study viral myocarditis, an inflammatory heart disease caused by viral infection. The project combines mathematical modeling with laboratory experiments to better understand how immune responses shape disease progression while providing ���ϲ����� undergraduate students with hands-on interdisciplinary research experiences in mathematics and biology.

Viral myocarditis is a potentially serious condition in which a viral infection triggers excessive inflammation that damages the heart. When the body detects the virus, it activates an immediate defense system called the innate immune response. That response is necessary for controlling the infection, but if it is too strong, lasts too long or occurs at the wrong time; the resulting inflammation can also damage heart tissue. Their project seeks to understand why the immune response sometimes protects the heart and, at other times, contributes to injury.

A mathematical model allows Ryu and Rivera-Serrano to create a simplified, virtual representation of what is happening inside the infected heart in ways that are currently impossible to achieve using biology and experiments alone. They will use equations to describe how the amount of virus changes over time, how different heart and immune cells respond, how those cells communicate through signaling molecules, and how those interactions influence inflammation and tissue damage.

“Our goal is to develop a mathematical model that integrates several biological processes occurring during viral myocarditis, including viral replication, infection and death of heart muscle cells, activation of antiviral defenses, recruitment of immune cells, inflammatory signaling and longer-term tissue damage,” said Ryu, associate professor of mathematics.

This will be a highly interdisciplinary project. Ryu, as a principal investigator, will lead the development, simulation and mathematical analysis of the model, while Rivera-Serrano, as a co-principal investigator, will provide expertise in virology, cell biology and innate immunity and will lead the experimental component.

“The mathematical and laboratory work will inform one another—experimental findings will help us make the model more biologically realistic, while predictions from the model will help us decide which biological interactions and hypotheses should be tested in the laboratory with undergraduate researchers here at ���ϲ�����,” Ryu said.

The project combines computational research, led by Ryu, with hands-on laboratory experiments, led by Rivera-Serrano.

“In the laboratory, we will grow heart and immune cells to examine how viral infection changes the behavior and biochemical signals produced and received by these distinct cell types,” Rivera-Serrano said. “We will measure outcomes such as viral infection and replication, cell survival or death, and the production of antiviral and inflammatory signaling molecules”.

These experiments will provide currently unavailable data that can be incorporated into the mathematical model and used to evaluate whether the model accurately reflects biological behavior. The process will also work in the other direction: if the model predicts that a particular cell type, signaling molecule or time point has an especially strong effect on inflammation, they can design experiments to test that prediction. Rather than treating the laboratory and mathematical components as separate projects, Ryu and Rivera-Serrano see them as a continuous feedback loop.

This research is important because the body needs a strong enough response to control the virus, but excessive or prolonged inflammation can weaken the heart, interfere with its electrical activity, and contribute to heart failure or other serious complications. Although many aspects of viral myocarditis have been studied, it remains difficult to understand how the different cardiac and immune cells communicate and how their interactions collectively shape disease progression over time.

“By combining mathematical modeling with laboratory experiments, we can gain insights into the immune response that neither approach could achieve independently,” Ryu said. “This allows us to integrate existing knowledge, identify the most influential biological mechanisms, and determine which questions are the most important to investigate experimentally. Ultimately, our goal is to provide researchers with a better roadmap for understanding when inflammation is protective and when it begins to damage the heart. That knowledge could guide future studies aimed at developing safer and more effective treatments for viral myocarditis.”

By the end of the project, Ryu and Rivera-Serrano hope to have developed and experimentally evaluated a mathematical framework that explains how viral replication, antiviral immunity, inflammatory signaling, and communication among heart and immune cells shape the progression of viral myocarditis.

Undergraduate research will be a central component to this project. Students from biology, mathematics, engineering and related STEM disciplines will be able to contribute according to their interests and expertise while also learning how researchers communicate and collaborate across disciplinary boundaries.

Students may help review scientific literature, design the model, estimate biological parameters, write and analyze computer simulations, conduct cell biology and biochemical experiments, analyze experimental data and compare laboratory findings with model predictions. They will also gain experience communicating their work through research presentations, national conferences and scientific publications.

“A particularly valuable aspect of the project is that students will not be limited to one narrow role,” Rivera-Serrano said. “A biology student may learn how experimental observations are converted into equations, while a mathematics or engineering student may learn how assumptions in a model correspond to actual cellular processes. Learning to communicate across disciplines is one of the most valuable skills students can develop for today’s biomedical research, where many important problems require expertise from multiple fields.”