PROJECT SUMMARY
Lack of appetite is a common symptom of acute and chronic inflammatory diseases. While this response is likely
adaptive in acute illness, in chronic diseases it may result in malnutrition leading to morbidity and mortality.
Inflammation-induced anorexia is mediated primarily by immune cell-secreted inflammatory cytokines. One of
the most potent and well-studied anorexigenic cytokines is interleukin-1ß (IL-1ß). Despite prolific literature on
this compound, the mechanism by which it signals to the brain to generate the psychological and behavioral
state of anorexia is incompletely understood. We have obtained preliminary data demonstrating that IL-1ß
influences the dynamics of canonical “hunger” neurons in the arcuate nucleus of the hypothalamus. Our current
proposal seeks to expand upon these initial observations by determining how peripherally administered IL-1ß
modulates the activity of deep brain nuclei to suppress food intake, focusing on contributions from peripheral
sensory neurons, especially vagal afferent populations. To accomplish this, we will use a suite of cutting-edge
tools including calcium imaging with fiber photometry, chemogenetic and behavioral approaches, and
microsurgical techniques. Our experiments will address how IL-1ß promotes anorexia at the circuit level with the
ultimate goal of revealing novel circuit-based therapeutic approaches to treat the nutritional complications of
inflammatory disease. In addition to completing the proposed experiments, this project will enable me to obtain
formal training in both scientific and professional areas. I will solidify my lab-based knowledge in computer
programming and immunology by attending workshops and taking courses in these areas. I will pursue
microsurgical training that will enable me to perform the complex surgeries required for this project. Finally, I will
gain valuable formal training in professional skills including mentorship and grantsmanship through workshops
and programs offered through the university. Taken together, completing the work outlined in this proposal will
leave me ideally positioned to obtain a postdoctoral fellowship in a top lab and ultimately a faculty position
where my lab will work at the intersection of neuroimmunology, metabolism and homeostasis.