Obiettivo
To make cell lines expressing cloned brain glutamate and glycine transporters, and to make antibodies to the transporters.
To investigate the ionic stoichiometry, molecular mechanism, oligomeric structure, regulation, pathological operation, and localisation of the transporters.
To terminate normal signal transmission in the brain, neurotransmitter is transported into neurones and glial cells by specialised molecules, the neurotransmitter uptake carriers. These transporters are also involved in brain pathology. For example, when the brain oxygen supply is reduced, glutamate carriers run backwards, releasing glutamate and thus triggering nerve cell death which causes mental and physical handicap. This project will study transporters for the major excitatory neurotransmitter glutamate, and for glycine, which is a major inhibitory transmitter and which also modulates the action of glutamate on one of its receptors. The work depends on combining the protein chemistry and molecular biology expertise of groups in Oslo, Madrid and Milan, who have isolated and cloned the transporters to be studied, with the expertise of groups in London and Paris, who have developed electrophysiological methods for studying the transporters in isolated cells and brain slices. Major aims are to produce cell lines expressing glutamate or glycine transporters and to analyse the properties of the transporters using electrical recording (patch-clamping). This will allow a detailed analysis of the molecular mechanism of transport, how the transporters are powered, how their activity is regulated, and under what conditions they run backwards releasing transmitter. The possible existence of hybrid glutamate transporters composed of subunits from different cloned transporters will be studied. Transporters will be localised at the cellular level using ion imaging, and at the subcellular level using antibodies.
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CSC - Cost-sharing contractsCoordinatore
WC1E 6BT London
Regno Unito