The kinase TOR is a key regulator of cell growth and organismal metabolism in animals. Consequently, the correct regulation
of TOR activity is important both for normal development and for disease. For instance, TOR is hyperactiva...
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Descripción del proyecto
The kinase TOR is a key regulator of cell growth and organismal metabolism in animals. Consequently, the correct regulation
of TOR activity is important both for normal development and for disease. For instance, TOR is hyperactivated in almost all
human cancers, and reduced TOR activity is associated with leanness and resistance to obesity. TOR activity is regulated
by a number of inputs including, importantly, amino acids. Indeed, nutritional amino-acid overload in humans is thought to
promote insulin resistance via TOR activation. However, the molecular mechanism by which amino acids regulate TOR is
still mysterious. I propose here to identify and characterize factors required for amino acids to regulate TOR. We will use
a 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 for
diagnosis 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 TOR
which we have implemented in my lab. In collaboration with the neighboring Boutros lab, we have performed a pilot screen on
the 780 kinases of the human genome, proving that the screen is working successfully, and yielding a number of interesting
hits which we have validated. The PhD student in my lab who performed the pilot screen is now characterizing these new
genes. I would like to fully exploit this platform by executing the screen on a genome-wide level, and following-up on the
genes that will be discovered. However, I do not have the necessary resources to do so. An ERC starting grant would allow
us to do this, leveraging our technology platform and the work we invested in creating it. I strongly believe these results will be
exciting and of general interest, helping to establish me in the field.