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Blending biophysical and drug discovery platforms to investigate allosterism in G-protein-coupled receptors (GPCRs) and find novel allosteric modulators for neurotherapeutics development (FATOKUNEUFP7IIF2010)
Start date: Aug 1, 2011, End date: Jul 31, 2013 PROJECT  FINISHED 

"The global socio-economic and health burden of neurological and neurodegenerative diseases is enormous, impacting overall quality of life and overwhelming available resources. The situation is worrying, considering the predicted future explosion in the aging population. There are currently no ideal drugs to manage these debilitating conditions. This project will thus achieve two major aims:1. Use biophysical approaches to improve fidelity of pharmacological observations of ligand-receptor interactions for determining mechanisms of action. This will allow investigations of such interactions at the single-cell level, as opposed to current investigations in cell populations, which are less accurate.2. Use the platform in aim 1 to develop screening assays to identify allosteric modulators of three receptors of exceptional clinical significance: adenosine, metabotropic and GABAB receptors. Allosteric modulators bind to a site on the receptor different from where the endogenous ligand binds, with better selectivity and reduced incidence of side effects compared to orthosteric modulators that bind to the same place as the endogenous ligand.The inter- and multi-disciplinary project combines pharmacology, biochemistry, molecular and cell biology, medicinal and synthetic chemistry, drug discovery and biophysics. It is intersectoral, featuring collaboration with a spin-out company (CellAura). Allosteric modulators would be developed as pharmacological tools or novel drugs in an arrangement that creates opportunities for longer-term collaboration with the USA, especially Johns Hopkins University.The Fellow will bring unique expertise in drug discovery and neuroscience. He will enhance his career prospect by engaging in a novel project different in focus and approach from what he undertook previously. The project will attain ERA objectives: product and technology development, patent ownership, product commercialization and creation of spin-outs and job opportunities."

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