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Molecular Neuroscience Research 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.
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