GPR52 signalling and structural biology

GPR52 is a brain-specific, orphan G protein-coupled receptor heavily implicated in CNS disorders, particularly schizophrenia. Using synthetic small molecule agonists, previous studies in our lab have identified the major signalling pathways downstream of the receptor in neurons, and the receptor’s role in striatal neurophysiology. However, little is known about the molecular and structural basis for small molecule activation of this important orphan receptor.

This project will
1. Extend these studies at the molecular level, using NanoLuc® Binary Technology (NanoBiT) to understand the preferred G protein-coupling of GPR52 in response to different synthetic small molecule agonists.
2. Investigate the expression and purification of GPR52 and appropriate G proteins in insect cells with the aim of forming G protein-bound complexes suitable for negative staining, single-particle cryo-EM, and structure determination.

Student will learn a range of techniques, including cell culture, transfections, cell signalling assays, and protein expression and purification.