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Molecular Neuroscience Research Group
Head of Research Group:
About the Group:
Our research group investigates the structure, function and regulation of two fast-acting ligand-gated ion channel neurotransmitter receptors, the major inhibitory GABAA receptor and the N-methyl-D-aspartate (NMDA) subclass of excitatory glutamate neurotransmitter receptor, important protein molecules pivotal to maintaining fidelity of brain function. For each of these receptors, multiple genes exist thus giving rise to the possibility of multiple receptor subtypes yielding potential novel targets for the development of new, receptor subtype-selective, therapeutic compounds for the treatment of stroke (NMDA receptors) and anxiety (GABAA receptors).
The aim is to delineate the molecular compositions, the pharmacological properties, the regulation, assembly and trafficking of these pivotal brain proteins using a combination of molecular biological and immunochemical techniques. Our research group is also interested in proteins which are associated with these receptors at synapses. These proteins are important in the targeting, trafficking and anchoring of receptor molecules in synaptic membranes. Again, they may be novel targets for pharmacological intervention. For example, the research group is studying how the post synaptic density 95 (PSD-95) MAGUK family of scaffold proteins regulates NMDA receptor subtype receptor expression, pharmacology, subcellular localization and lateral mobility. More recently, the research group has discovered using the yeast two-hybrid system a new family of coiled-coil proteins that are putative GABAA receptor trafficking molecules, GRIF-1 (GABAA receptor interacting factor, also termed TRAK2) and TRAK1. GRIF-1 is only expressed in excitable tissues such as the brain, the heart and skeletal muscle. It is a kinesin-adaptor protein that also mediates anterograde trafficking of mitochondria and other organelles to synapses. Work is ongoing to determine the role that GRIF-1 plays in receptor and mitochondrial trafficking in neurones.
Our research group is expert in the production of receptor subtype-selective antibodies. We have provided many laboratories world wide with these important research tools. In particular, the research group has close collaboration with Professor Peter Somogyi FRS and colleagues of the MRC Anatomical Neuropharmacology Unit in Oxford, UK, to determine the sub-cellular distributions of these receptor subtypes and Dr Daniel Choquet's group at the CNRS Physiologie Cellulaire de la Synapse Unit in Bordeaux, France to investigate the lateral mobility of NMDA receptor subtypes. Other collaborators include Professor Nick Hartell, University of Leicester and Dr Michael Perkinton, Kings College, London.
Research Group Members:
- Dr Kieran Brickley, Postdoctoral researcher.
- Dr Sarah Cousins, Postdoctoral researcher.
- Dr Neal Innocent, Alzheimer's Research Trust Fellow.
- Dr Caroline Hatchett, Postdoctoral researcher (Joint appointment with Dr Jasmina Jovanovic)
- Tom Randall, Bloomsbury PhD student (Joint with Dr Carolyn Moores, Birkbeck College)
- BBSRC Project Grant "Assembly and targeting of NMDA receptors and their accessory scaffolding proteins"
- BBSRC Project Grant “OIP106 (TRAK1) and GRIF-1 (TRAK2), kinesin-associated adaptor proteins: a study of their role in mitochondrial trafficking processes in neurones.
- With Professor Nick Hartell, University of Leicester BBSRC Project Grant "Use of a ratiometric pH sensor for the live imaging of transmitter release in the CNS".
- BBSRC Project Grant ""An investigation into NMDA receptor subtype synaptic targeting and later-al mobility mediated by the PSD-95 MAGUK family of scaffold proteins."
- Alzheimer Research Trust “Amyloid precursor protein: a novel role in the regulation of NMDA receptor surface trafficking: a biochemical investigation".
- With Drs A Ali, K Harvey, J Jovanovic, A Mercer, B Pearce, and Professors RJ Harvey and AM Thomson, Medical Research Council, "Mechanisms underlying synapse-specific clustering of GABAA receptors" .
- With Professors AM Thomson and RJ Harvey and Drs A Ruiz and M Shah. The Wellcome Trust, "Establishing an advanced imaging facility for neuroscience" .
Current Activities of Recent Group Members:
Dr Mike Beck, a DAAD Visiting Research Fellow, has returned to Germany where he is working as a Post-doctoral Fellow at :- Max-Planck-Institute for Molecular Cell Biology and Genetics Pfotenhauerstr. 108, D-01307 Dresden, Germany.
Dr Lynda M Hawkins, Lecturer, North Devon College, Barnstaple.
Recent members who have obtained a PhD:
Dr Bela Chopra is now a Research Scientist at BioFocus Discovery Ltd., Cambridge, UK
Dr Gurmail Ojla is a Global Applications Specialist for the multiviewers confocal system, Perkin Elmer, UK.
Dr Michalis Papadakis is a Post-Doctoral Research Fellow at the University of Oxford, UK.
Dr Karino Pozo is a Post-Doctoral Research Fellow at the MRC Laboratory for Molecular Cell Biology, University College, London, UK
Dr A Richard Rutter is now Biochemistry Team Leader at the NGI CEDD R & D Centre, SIngapore
Dr Seema Sharma is European Programme Director for Science's Next Wave in Cambridge, UK.
Dr Miriam Smith is a Post-doctoral Research Fellow at Massachusetts General Hospital and Harvard Medical School, USA.
Page last modified on 13 may 13 16:36