Cystallisation of the Multifunctional Receptor Clustering Protein Gephyrin

Supervisor                       Dr Kirsten Harvey (SoP)

Co-Supervisor                 Professor Nicholas Keep (Bbk)

Applications are invited for a three year Bloomsbury Colleges PhD Studentship in the laboratories of Dr Kirsten Harvey at the School of Pharmacy, University of London and Professor Nicholas Keep at Birkbeck, University of London.  This joint studentship PhD project aims to combine structural, molecular and cell biological approaches to elucidate the basis of GABA-A receptor clustering at synapses by the clustering protein gephyrin in more detail.  GABA-A receptors are the most abundant type of inhibitory receptor in the brain and are the pharmacological targets of benzodiazepines, barbituates and volatile anaesthetics.  The correct positioning of selected GABA-A receptor subtypes at synapses is determined by a set of trafficking and clustering proteins including gephyrin and collybistin.  Mislocation of neuronal GABA-A receptors can result in epileptic seizures, mental retardation and increased anxiety.

The successful candidate will work jointly in an established research group at the School of Pharmacy and at the Institute of Structural and Molecular Biology at Birkbeck/UCL.  This project will allow the development of skills in structural biology, proteomics and cell biology.  The PhD Studentships will be enhanced by the provision of specialized training courses available at both academic institutions.  The successful candidates will have access to excellent molecular biology, cell biological, structural and computational facilities.

Applicants must have or be expected to achieve at least a 2.1 degree in a relevant subject and be of home or EU status.  The PhD Studentship stipend will be in accord with BBSRC rates including a London allowance.

Key References

1.   Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Lüscher B, Res MI and Harvey RJ (2004) The GDP-GTP exchange factor collybistin:  An essential determinant of neuronal gephyrin clustering.  J Neuroscience 24: 5816-5826.
2.  Kalscheuer VM, Musante L, Fang C, Hoffman K, Fuchs C, Carta E, Deas E, Venkateswarlu K, Menzel C, Ullmann R, Tommerup N, Dalprà L, Tzschach A, Selicorni A, Lüscher B, Ropers HH, HarveyK, Harvey RJ (2009) A balanced chromosomal translocation disrupting ARHGEF9 is associated with epilepsy, anxiety, aggression and mental retardation.  Human Mutation 30: 61-68..
3.  Knight D, Harris R, McAlister MSB, Phelan JP, Geddes S, Moss SJ, Driscoll PC and Keep, NH (2002) The X-ray crystal structure and putative ligand-derived peptide-binding properties of GABAA receptor associated protein (GABARAP). J.Biol. Chem 277: 5556-5561.
4.  Fritschy JM, Harvey RJ, Schwarz (2008) Gephyrin: where do we stand, where do we go? Trends Neurosci. 31:  257-264.

Further details about the project may be obtained from:

Supervisor:          Dr Kirsten Harvey, kirsten.harvey@pharmacy.ac.uk
http://www.pharmacy.ac.uk/kirsten_harvey.html

Co-Supervisor:    Professor Nicholas Keep, n.keep@mail.cryst.bbk.ac.uk
http://people.cryst.bbk.ac.uk/~ubcg48a/

Further information about PhDs at The School of Pharmacy and Birkbeck is available from:

http://www.pharmacy.ac.uk/1565.html
http://www.bbk.ac.uk/prospective/research/
htttp://www.cryst.bbk.ac.uk./phd.html

Application forms and details about how to apply are available from:

http://www.pharmacy.ac.uk/apply_msc100.html

The Registrar
The School of Pharmacy
University of London
29-39 Brunswick Square London
WC1N 1AX
UK.
Tel 00 04 (0)20 7753 5958
Fax: 00 04 (0)20 7753 5829
E-mail: registry@pharmacy.ac.uk

To apply, please send a completed Postgraduate Application Form (http://www.pharmacy.ac.uk/fileadmin/documents/msc/postgrad-appform-new.pdf) to the Registrar at the address above.

Closing date for applications is: 1st March 2010

 

The Bloomsbury Colleges, University of London: Birkbeck; Institute of Education; London School of Hygiene & Tropical Medicine; School of Oriental and African Studies; The School of Pharmacy; Royal Veterinary College.