Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
Abstract Intestinal stem cells (ISCs) play pivotal roles in intestinal epithelium renewal during homeostasis and after injury. The metabolic demands faced by ISCs require high mitochondrial oxidative phosphorylation (OXPHOS) activity compared to other differentiated cells. ISCs’ mitochondrial dysfunction has been implicated in the etiopathogenesis of intestinal bowel diseases (IBD), which afflicts over 2 million people in the US. The carbon sources that fuel ISC OXPHOS have been broadly described in the small intestine (SI) but not in the colon. I seek to understand how ISC metabolic demands are met in the colon. The colonic epithelium is organized into the colonic crypt. ISCs localize to the base of the crypt (base-crypt), and this protects them from microbial metabolites and microbe-associated molecular patterns (MAMPs). Top-crypt differentiated colonic epithelial cells (CECs) oxidize microbial-derived short-chain fatty acid (SCFA) butyrate making it inaccessible to base-crypt cells. This shields ISCs, as butyrate suppresses ISC proliferation. This metabolic interaction between CECs and ISCs has focused my interest in CEC-ISC metabolic cross-talk. Ketones (acetoacetate, β-hydroxybutyric acid (βHB), and acetone) are important metabolic substrates. I hypothesize that CECs generate ketones that are used by ISCs as their principal energy source. This hypothesis is supported by the localization of rate-limiting enzymes (RLE) for the generation of ketones to the CECs and my preliminary data demonstrating that loss of these enzymes in CECs compromises ISC self-renewal and differentiation. My proposal focuses on this metabolic cooperation between epithelial cells within the crypt where top-crypt CECs shuttle ketones to base-crypt ISCs thus maintaining their turnover capacity. Understanding colonic ketone biosynthesis and function could lead to new treatments and therapeutic targets for IBD. Beyond defining this proposed metabolic crosstalk between CEC and ISC, I am interested in factors regulating CEC metabolic enzymes. I have identified microbial features that regulate the expression of the CEC RLE for ketone generation. I will determine the receptor and pathways downstream of this receptor by which they regulate the expression of this RLE. This research will help to decipher how microbial signals and metabolites contribute to epithelial repair and regeneration.
Grant Summary
Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $38K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $38K
2028-04-30
- 1Confirm your organization is eligible for Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon: Frequently Asked Questions
Who is eligible for the Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon?
Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon provide?
Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon provides up to $38K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon deadline?
Applications for Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon?
To apply for Understanding the Role and Regulation of Epithelial Ketogenesis in the Colon, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.