Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon

Summary

This research aims to understand how intestinal stem cells in the colon meet their metabolic demands, specifically hypothesizing that colonic epithelial cells generate and shuttle ketones to stem cells as an energy source, and to identify microbial factors regulating this process.

What they want

The project will investigate the metabolic cooperation between top-crypt colonic epithelial cells (CECs) and base-crypt intestinal stem cells (ISCs), focusing on the hypothesis that CECs generate ketones (acetoacetate, β-hydroxybutyric acid, and acetone) which are then utilized by ISCs as their primary energy source. This includes defining the proposed metabolic crosstalk and identifying the receptor and downstream pathways through which microbial features regulate the expression of rate-limiting enzymes for ketone generation in CECs.

Deliverables

Understanding colonic ketone biosynthesis and function
Identification of new treatments and therapeutic targets for Inflammatory Bowel Disease (IBD)
Deciphering how microbial signals and metabolites contribute to epithelial repair and regeneration
Characterization of the receptor and pathways regulating CEC metabolic enzymes