Grant: Project Grant

It has long been known that our intestines are host to a wide diversity of microorganisms that play major roles in the digestion of food. However, recent research has shown that many of these bacteria also play important roles in regulating other body functions, including hunger, metabolism, immunity, inflammation and even behaviour. The identity of the specific bacteria and byproducts that mediate these activities is largely unknown. We hypothesize that a family of proteins called nuclear receptors, already known for their roles in metabolism, immunity and inflammation, and that do so under the control of small molecules like those produced in the gut, act as hormonal mediators of these signals. Our approach for testing this hypothesis includes the generation of small molecule extracts from gut tissues and contents and using each of the 48 human nuclear receptor proteins to specifically isolate those that bind tightly and specifically. We will then identify these molecules using new technologies perfected by our team that identify their composition and structures based on their exact mass. Our subsequent analyses of their molecular and physiological consequences will focus primarily on a limited number of selected molecules and their roles in preventing or causing bowel inflammatory disorders. However, the full list of identified molecules and microbe sources will be made publicly available to all researchers in all areas of study in order to fully leverage the benefits of our work. The identification of these new molecules and interactions will provide a major leap forward in our understanding of how the organisms in our gut affect our physiology, as well as providing new probiotic tools to control a wide range of diseases.