Single Molecule Approaches to Study G protein Activation and Arrestin Recruitment by B1 adrenergic receptor

The pharmacology of a cell surface G protein-coupled receptor (GPCR) is dependent on the kinetics of ligand binding. However, little is known how ligand binding kinetics modulate the kinetics of recruiting signalling proteins by the receptors. The project aims to study the kinetics of G protein activation and arrestin recruitment by Beta1-adrenergic receptor in both living cells and reconstituted system consisting of purified receptor nanoparticles and signalling proteins as a function pharmacological properties of agonists. The student will develop fluorescent versions of receptors, G proteins and arrestins and use these constructs to study the processes of G protein activation and arresting recruitment with single molecule techniques. They will investigate how ligands with different binding kinetics, different efficacies and different pharmacology affect receptor signalling properties. The project offers an opportunity to develop advanced protein engineering and protein production skills and expertise in the state-of-the-art biophysical methods