Systems Approaches to the mTOR Network
Mammalian target of rapamycin (mTOR) kinase is a central controller of cellular growth and metabolism. mTOR is regulated by nutrients, growth factors, and stress, and acts in two structurally and functionally distinct multiprotein complexes, termed mTOR complex 1 (mTORC1) and mTORC2. Many tumors display mTOR dysregulation, making mTOR a prime target in cancer therapy. Our lab studies the control of metabolic homeostasis by mTOR by cell biology, biochemistry, proteomics, and systems modeling.
In my presentation, I will discuss our most recent advances to dissect amino acid signaling and stress inputs to the mTOR network by combined computational modeling and experimental strategies.
1. Dalle Pezze, P., et al. A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nature Communications 7, 13254 (2016).
2. Thedieck, K., et al. Inhibition of mTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells. Cell 154, 859-874 (2013).
3. Sonntag, A.G., Dalle Pezze, P., Shanley, D.P. & Thedieck, K. A modelling-experimental approach reveals insulin receptor substrate (IRS)-dependent regulation of adenosine monosphosphate-dependent kinase (AMPK) by insulin. FEBS J 279, 3314-3328 (2012).
4. Dalle Pezze, P., et al. A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation. Science signaling 5, ra25 (2012).