Research

We are pursuing a number of projects designed to understand the key pathways that regulate incretin receptor output at the molecular level. 

Some of our current projects include:

• Identification of the main endocytic trafficking pathways that control GLP-1 receptor signalling in pancreatic beta cells
• Control of GLP-1 receptor trafficking and signalling by modified (including biased) agonists
• The role of β-arrestin-2 in the spatiotemporal control of GLP-1 receptor signalling in vivo
• Mechanisms of GLP-1 receptor plasma membrane diffusion, clustering and segregation to lipid nanodomains
• Study of GLP-1 receptor post-translational modifications, including agonist-induced receptor palmitoylation, phosphorylation and ubiquitination
• Regulation of beta cell GLP-1 receptor responses by the lipid microenvironment, including identification of cholesterol binding sites
• Differences in spatiotemporal regulation of signalling of GLP-1 receptor versus GIP receptor in beta cells
• Biased agonist control of endogenous GLP-1 receptor trafficking and signalling in intact islets
• Tissue selectivity of GLP-1 receptor agonist responses in neurons versus pancreas
• Analysis of changes in spatiotemporal signalling and agonist responses associated with the GLP-1 receptor genetic variant rs10305492
• Mass spectrometry-based analysis of the GLP-1R interactome
• Analysis of GIPR genetic variants in pancreatic beta cells and adipocytes