With respiratory illness season in full swing, a bad night's sleep, sore throat, and desire to cancel dinner plans could all be considered hallmark symptoms of the flu, Covid-19 or other illnesses. Although everyone has, at some point, experienced illness and these stereotypical symptoms, the mechanisms that generate them are not well understood.
Zuri Sullivan , a new assistant professor in the MIT Department of Biology and core member of the Whitehead Institute for Biomedical Research, works at the interface of neuroscience, microbiology, physiology, and immunology to study the biological workings underlying illness. In this interview, she describes her work on immunity thus far as well as research avenues - and professional collaborations - she's excited to explore at MIT.
Q: What is immunity, and why do we get sick in the first place?
A: We can think of immunity in two ways: the antimicrobial programs that defend against a pathogen directly, and sickness, the altered organismal state that happens when we get an infection.
Sickness itself arises from brain-immune system interaction. The immune system is talking to the brain, and then the brain has a system-wide impact on host defense via its ability to have top-down control of physiologic systems and behavior. People might assume that sickness is an unintended consequence of infection, that it happens because your immune system is active, but we hypothesize that it's likely an adaptive process that contributes to host defense.
If we consider sickness as immunity at the organismal scale, I think of my work as bridging the dynamic immunological processes that occur at the cellular scale, the tissue scale, and the organismal scale. I'm interested in the molecular and cellular mechanisms by which the immune system communicates with the brain to generate changes in behavior and physiology, such as fever, loss of appetite, and changes in social interaction.
Q: What sickness behaviors fascinate you?
A: During my thesis work at Yale University, I studied how the gut processes different nutrients and the role of the immune system in regulating gut homeostasis in response to different kinds of food. I'm especially interested in the interaction between food, the immune system, and the brain. One of the things I'm most excited about is the reduction in appetite, or changes in food choice, because we have what I would consider pretty strong evidence that these may be adaptive.
Sleep is another area we're interested in exploring. From their own subjective experience, everyone knows that sleep is often altered during infection.
I also don't just want to examine snapshots in time. I want to characterize changes over the course of an infection. There's probably going to be individual variability, which I think may be in part because pathogens are also changing over the course of an illness - we're studying two different biological systems interacting with each other.
Q: What sorts of expertise are you hoping to recruit to your lab, and what collaborations are you excited about pursuing?
A: I really want to bring together different areas of biology to think about organism-wide questions. The thing that's most important to me is people who are creative - I'd rather trainees come in with an interesting idea than a perfectly formed question within the bounds of what we already believe to be true. I'm also interested in people who would complement my expertise; I'm fascinated by microbiology, but I don't have any formal training.
The Whitehead Institute is really invested in interdisciplinary work, and there's a natural synergy between my work and the other labs in this small community at the Whitehead Institute.
I've been collaborating with Sebastian Lourido's lab for a few years, looking at how Toxoplasma gondii influences social behavior, and I'm excited to invest more time in that project. I'm also interested in molecular neuroscience, which is a focus of Siniša Hrvatin's lab . That lab is interested in the hypothalamus, and trying to understand the mechanisms that generate torpor. My work also focuses on the hypothalamus because it regulates homeostatic behaviors that change during sickness, such as appetite, sleep, social behavior, and body temperature.
By studying different sickness states generated by different kinds of pathogens - parasites, viruses, bacteria - we can ask really interesting questions about how and why we get sick.
