Chemoproteomic discovery and functional analysis microbiota bile acid-protein targets in host immunity

PROJECT SUMMARY Key metabolites from intestinal microbiota can modulate host immune responses, but their mechanisms of action are unclear and limit the development of new therapeutic approaches in human health and disease. To determine the mechanism(s) of action of prominent microbiota metabolites (short chain fatty acids, aromatic amino acids, bile acids and others), multi-disciplinary approaches are needed to biochemically identify metabolite-protein targets in mammalian cells and characterize their activity on host immunity in vivo. For this grant application, our laboratories will focus on microbiota-associated bile acids and employ innovative methods in chemical biology and proteomics to identify their protein targets in mammalian cells and characterize their mechanism(s) of action on host immunity in vitro, ex vivo and in mouse models in vivo. A better understanding of how these microbiota metabolites affects host immunity should reveal potential therapeutic targets and facilitate the development of therapeutic approaches against infection and cancer in animals and humans.