Kennedy, Mia

Project title: Investigating the role of the short-chain fatty acid isovalerate on intestinal immune responses

Department: Biochemistry and Microbiology

Faculty supervisor: Dr. Lisa Reynolds

"Our laboratory investigates the relationship between parasitic worms (helminths), the intestinal microbiota, and the immune system. Helminths have evolved mechanisms to alter our immune system in order to maintain chronic infections in their host. Some of these mechanisms work to suppress the onslaught of the immune response against them, and if elucidated, could offer potential treatment for inflammatory disorders or autoimmune diseases.

My project will explore one possible immunomodulatory mechanism employed by a helminth, previously identified in our laboratory. Through metabolite analysis it was found that levels of the short-chain fatty acid (SCFA) isovaleric acid are elevated during a helminth infection, and return to baseline upon clearance of the helminth. I will be working under the hypothesis that the helminth directly increases the levels of isovaleric acid in order to promote its survival in the host.

To test whether our model helminth directly produces isovaleric acid, I will culture helminths with various amino acid substrates that can be broken down to produce isovaleric acid, and will then measure isovaleric acid levels. To test whether isovaleric acid levels promote helminth survival, I will track the ability of mice to expel helminths after mice have been supplemented with or without isovaleric acid. To measure the ability of mice to expel helminths I will track helminth egg output in feces, enumerate adult worms in the intestinal tract after several weeks of infection, and measure the immune response of mice using flow cytometry."