MRC National Institute for Medical Research, London
Science for Health
NIMR sandwich student success
04 March 2011
Rob Kaye is studying for a BSc in medical physiology at the University of Leicester and chose to take the 'Year in Industry' option. He spent the year as a sandwich student at NIMR, 2009-10, working in Ed Hulme's lab in the Division of Physical Biochemistry.
Rob and his colleagues used alanine-scanning mutagenesis followed by functional expression and molecular modelling to analyse the role of the 14 residues Asn422-Cys435 C-terminal to trans-membrane helix 7 of the M1 muscarinic acetylcholine receptor. The results suggest that they form an 8th (H8) helix, associated with the cytoplasmic surface of the cell membrane in the active state of the receptor.
The results of his work have now been published in Molecular Pharmacology with Rob listed as the first author. Rob also received a bursary to present his findings at the London Meeting of the British Pharmacological Society in December 2010.
This is an exciting time for those of us who are interested in G protein- coupled receptors, key targets for drug discovery. Rob's study used scanning mutagenesis to study the function of the cytoplasmic membrane-associated helix 8 of the M1 muscarinic receptor, completing a project initiated by a previous post-doc. The results suggested that H8 is the initial docking station for receptor-G protein encounter. This provides an important insight into GPCR structure-function relationships.
Ed Hulme
There is no better way to put the lab skills learned in the first few years of your university degree into practice than to spend up to 12 months working in a research lab. Sandwich students come to the Institute because of the diversity of science and to get a better feel of whether research is really for them. Many of our sandwich students go on to do a PhD at NIMR or another leading research institute.
Donna Brown
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Proposed G protein contact residues in H8 and elsewhere in (a) bovine rhodopsin (b) the M1 mAChR homology model and (c) the bovine opsin-transducin peptide complex.
Original article
Kaye, RG; Saldanha, JW; Lu, Z-L and Hulme, EC (2011)
Helix 8 of the M1 muscarinic acetylcholine receptor: scanning mutagenesis delineates a G protein recognition site.
Molecular Pharmacology Epub ahead of print. Publisher abstract
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