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