Project Reference: TRG27-IMS-FR1

Project title: Mechanisms of GLP-1 secretion from human intestinal organoids

Project outline

GLP-1 based drugs are well-recognised treatments for obesity and diabetes, that mimic the body’s own gut-brain axis. Endogenous GLP-1 is produced by L-cells located in the intestinal epithelium, which sense nutrient ingestion and generate hormonal signals related to the quality and quantity of nutrients being absorbed. This project will investigate the intracellular signalling events leading to secretion of GLP-1 containing vesicles from human L-cells, with a focus on characterising proteins involved in regulated vesicular exocytosis downstream of calcium and cAMP signals. Exocytosis will be monitored by electrophysiology (capacitance), live cell imaging and measurements of hormone secretion. Proteins of interest will be identified by function, transcriptomics and pharmacology, and confirmed by creating gene knockouts in the organoids using CRISPR-Cas9. Understanding L-cell release mechanisms will help in the design of drugs and diet to treat conditions such as obesity and irritable bowel syndrome. 

Principal Supervisor

Professor Frank Reimann

Email address: fr222@cam.ac.uk

Department / Partner Institute: Institute of Metabolic Science (IMS)

Website: https://www.mrl.ims.cam.ac.uk/staff/professor-frank-reimann

BBSRC strategic theme

Understanding the rules of life