Mapping G Protein Coupled Receptor Interactions using Carbene Footprinting
A BBSRC iCASE PhD studentship is available to work with Prof Neil Oldham at the University of Nottingham in collaboration with OMass Technologies. The project will focus on the use of photoactivatable diazirine probes and mass spectrometry to footprint G-protein coupled receptors (GPCRs) in order to map interactions and identify conformational changes.
GPCRs are a large group of membrane-bound receptors which are of major importance for signal transduction in eukaryotic organisms. They are responsible for the detection of extracellular ligands and promoting down-stream signal transduction. As their name suggests, they are found in association with G protein assemblies, which carry the signal to the interior of cell. GCPRs possess a conserved 7-pass transmembrane helical structure. Upon ligand binding, a conformational shift is induced. This causes disassembly of the associated G protein complex and propagation of the signal through either the cAMP or phosphatidylinositol pathways.
Recently, we have developed a probe for efficient photochemical footprinting of membrane proteins. Mass spectrometry, a powerful analytical technique, is used to identify the locations of probe attachment, and hence surface accessible regions. This approach will be used map GPCR interactions with small molecule ligands and G protein.
Candidates should hold, or expect to hold, a first or upper second class degree in chemistry or biochemistry and have a strong interest in biological mass spectrometry.
Informal enquiries may be addressed to Prof Neil Oldham, neil.oldham@nottingham.ac.uk.
Click here to apply for this project.