Project Grant R01AI194527

This project grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) supports investigative research into the complex nonlinear dynamics governing tuft cell-microbiome interactions and their role in immune regulation. The University of Massachusetts Medical School received $836,691 in obligated funding (awarded June 17, 2026, with completion anticipated by May 30, 2031) to conduct mathematical modeling and experimental validation studies examining how feedback loops between tuft cells, intestinal microbiota, and immune cells collectively optimize intestinal homeostasis and resilience. The research specifically investigates how tuft cells sense succinate—a microbial metabolite produced by succinate-producing bacteria—and respond by secreting interleukin-25 to activate type 2 lymphocytes, creating a self-reinforcing feedback mechanism that protects against pathogen-induced colitis while preventing uncontrolled inflammation.

The project combines computational modeling with laboratory-based experimental research to elucidate how epithelial-immune-microbiome interactions form coordinated feedback loops that enable the intestinal system to flexibly transition between homeostatic and hyperplastic states. The research examines how tuft cells actively promote colonization by beneficial microbes while other epithelial cell types such as goblet cells and Paneth cells may exert complementary or counterbalancing influences. The project's outcomes will advance understanding of intestinal mucosal immunology and may inform therapeutic approaches to infectious diseases, inflammatory conditions, and immune-mediated disorders.