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Amino acid sensing by TOR (TOR-AA)
Start date: Sep 1, 2010, End date: Aug 31, 2015 PROJECT  FINISHED 

The kinase TOR is a key regulator of cell growth and organismal metabolism in animals. Consequently, the correct regulationof TOR activity is important both for normal development and for disease. For instance, TOR is hyperactivated in almost allhuman cancers, and reduced TOR activity is associated with leanness and resistance to obesity. TOR activity is regulatedby a number of inputs including, importantly, amino acids. Indeed, nutritional amino-acid overload in humans is thought topromote insulin resistance via TOR activation. However, the molecular mechanism by which amino acids regulate TOR isstill mysterious. I propose here to identify and characterize factors required for amino acids to regulate TOR. We will usea genome-wide functional-genomics approach to systematically identify a large number of genes involved in this process,thereby hopefully making a significant contribution to the field. Identification of these novel factors may open avenues fordiagnosis and treatment of cancer and metabolic disease.This project will exploit a high-throughput, cell-based screen for genes involved specifically in amino acid sensing by TORwhich we have implemented in my lab. In collaboration with the neighboring Boutros lab, we have performed a pilot screen onthe 780 kinases of the human genome, proving that the screen is working successfully, and yielding a number of interestinghits which we have validated. The PhD student in my lab who performed the pilot screen is now characterizing these newgenes. I would like to fully exploit this platform by executing the screen on a genome-wide level, and following-up on thegenes that will be discovered. However, I do not have the necessary resources to do so. An ERC starting grant would allowus to do this, leveraging our technology platform and the work we invested in creating it. I strongly believe these results will beexciting and of general interest, helping to establish me in the field.

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