Wellcome Trust Clinical PhD Programme at Imperial College London (360G-Wellcome-097880_Z_11_Z)

Glucagon (GCG) is a natural pancreatic hormone that controls carbohydrate and fat metabolism, suppresses appetite, increases energy expenditure and stimulates insulin secretion. Recently, it has been found that the glucagon receptor (GCG-R) may interact with RAMP2, a member of the family of Receptor Activity-Modifying Proteins, which are accessory transmembrane proteins that associate with Class II G-protein coupled receptors (GPCRs) to alter their ligand binding properties. This project aims to study the interaction of GCG-R with RAMP2, with the following goals: 1. To prove that RAMP2 and GCG-R interact directly. 2. To understand the effect of this interaction on the binding of GCG by GCG-R. 3. To understand the effect of this interaction on the activation of GCG-R by GCG. 4. To understand the role this interaction plays in the co-localisation of GCG-R and RAMP2 in the cell membrane. An understanding of the role that RAMP2 plays in modifying the function of GCG-R may assist in devising a selective agonist of GCG-R that possesses therapeutically desirable properties (e.g. appetite suppression, increase in energy expenditure) without undesirable properties (e.g. increasing hepatic glucose output).