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.
Funding Notes
Funding: This is available as a self-funded project. In addition to fees and student living expenses, the work requires bench fee support of £12,000 p.a.
Entry Requirements: Candidates must have a first or upper second class honors degree or significant research experience.
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