The NSF-Simons National Institute for Theory and Mathematics in Biology is composed of investigators at the forefront of innovative research at the interface of mathematics and biology. Each member of the NSF-Simons NITMB brings a unique perspective that is vital for achieving the NITMB’s mission to develop new mathematics and inspire biological discovery. In order to highlight the diversity of expertise present, and the valuable contributions of NITMB members, the NITMB will be sharing insight into one of our members every month.
Sarah Cobey is a Professor of Ecology and Evolution at the University of Chicago. The Cobey Lab investigates the coevolution of pathogens and hosts’ adaptive immunity. Cobey’s group uses computational and mathematical tools to test hypotheses and advance theory.
We spoke with Sarah Cobey to learn more about her work and the exciting future trajectories for pathogen evolution research.
What is your current research area?
“One of the big questions we’re tackling is, ‘how does host immunity regulate pathogen populations?’ We’re focused on fast-evolving respiratory viruses, including influenza and SARS-CoV2. We want to understand how immunity from infections and vaccinations influences their epidemiological (i.e., population) and evolutionary dynamics. We try to connect immune dynamics to individuals in global patterns.”
What disciplines does your research integrate?
“Our foundation is ecology and evolution. We collaborate with immunologists, virologists, and field epidemiologists to design studies to test our hypotheses. We also work with experts in causal inference, and we are always interested in better ways to model and forecast stochastic nonlinear dynamical systems.”
Where do you find inspiration?
“It’s really not hard! The COVID-19 pandemic has brought many deep questions into public discussion. Should we continue to expect major evolutionary innovations with SARS-CoV-2, as we first saw with Omicron? Will we have many cocirculating variants in the future? Is it possible for vaccines to direct our immune responses better, so we learn to recognize new parts of the virus faster? Why is there so much variability in individual responses to infection and vaccination? Where does that variability come from, and how does it affect epidemic and evolutionary dynamics? Finally, why do epidemics of different respiratory pathogens peak when they do?”
What aspects of your research could be interesting to mathematicians or applied to biology?
“I wish I had time to list them all. Within hosts, it's unclear how much chance plays a role in the evolution of antibodies that bind to specific parts of a virus. Understanding this is critically important for vaccination strategy and just plain interesting for thinking about the evolution of immune systems. Relatedly, it's unclear what the fundamental constraints are on adaptive immune responses. At the population level, we still don't understand how respiratory pathogens interact indirectly or what explains their seasonality. Those are tremendous inference and prediction problems.”
What about the NITMB do you find exciting?
“I'm excited to step back and think more broadly about quantitative approaches and translational biological themes. My field has been in emergency mode these past few years, which has led to a certain insularity, and I'm grateful for getting the chance to come up for breath intellectually. I hope the break lasts.”
What career achievement are you most proud of?
“Two leap to mind, but it's hard to pick. I'm proud I've learned some immunology (I can fool certain kinds of immunologists for a few minutes) and especially happy that my mathematical models seem to have affected how some immunologists think about problems. My background is theory and computation, usually of observational data, and I'm also proud that I've gotten to a place where I am running a large experiment (a randomized clinical trial) and helping guide the design and analysis of other studies.”
Outside of your research, what other interests do you have?
“I'm trying to get a planted freshwater aquarium set up in the lab. It's reminding me that my training is in theory.”
What are you hoping to work on in the future?
“We have our hands full for a while. Currently we are working on studies related to the effects of repeated vaccination and the correct estimation of vaccine effectiveness, and we'll be analyzing the first real wave of results from our randomized clinical trial this year. I'm also excited about a nascent collaboration that would allow us to measure population immunity over decades. Quantifying population immunity this way could allow us to test directly how deterministic the evolution of viruses really is, and we could learn more about which age groups are driving transmission, and much else.”
The NITMB is proud to have Sarah Cobey as a valued member of the Institute. More information on Professor Cobey’s work can be found on the Cobey Lab website.