Current Research Interests
Our current interests are focussed on GPCRs, in particular the neurotensin type 1 receptor. We have improved expression and purification yields using immunofluorescence methods, and characterized its ligand binding using novel SPR methods. Reconstitution into lipid bilayers in a ligand binding form has now been resolved, and fluorescent methods (FRET) used to demonstrate the constituititive dimerization of the receptor. Magnetic resonance methods are being used to understand the activation mechanism by the ligand, NT, which is a 13-mer peptide - only the terminal six residues are required for receptor activation. By spin labelling, either with 13C, 15N, or nitroxides in the non-binding region of NT, the dynamics of bound NT and its electronic environment in the receptor binding site are being probed. Homology modelling and docking algorithms are being tested by the experimental data being generated. Single molecule methods, including AFM and cryo-EM, and hydrodynamic methods such as SANS and AUC, are being used to probe the dimerization and conformational changes on activation through ligand binding.