Novel G Protein-Coupled Receptor interactions with RAMP accessory proteins

Cell signalling is critical to multicellular organisms and underlies physiology and diseases. Understanding of the ways cells sense and respond to hormones and growth factors is a constantly-evolving field. Mammals use just over 700 G Protein-Coupled Receptors (GPCRs) to perceive endocrine and paracrine signals, but the mechanisms of receptor responses are complex. A family of accessory proteins (receptor activity modifying proteins or RAMPs) was discovered 20 years ago and until recently were thought to be involved in modifying signalling in a small number of receptors. However it is now becoming clear that RAMPs regulate receptor trafficking, ligand selectivity and signalling in a much larger number of GPCRs. This project is to determine the role of the RAMPs in altering signalling responses in association with novel GPCR partners. The work will involve a wide range of techniques from molecular and cell biology including determination of expression of RNA and protein for GPCRs and RAMPs, cellular localisation by FRET/BRET and functional studies of signalling activation. In collaboration with Sheffield’s crystallographers, we hope to determine structures of novel GPCR/RAMP partners and to test a library of antagonist and agonist chemical fragments and compounds on signalling.
This project will provide a training in a range of transferrable skills in a in a well-funded and enthusiastic group of academics, postdocs and students with a wide experience in successful supervision of PhD studies.