The Rat sarcoma (Ras) small G-protein is a signal transduction protein which enables cells to communicate ‘biological signals’ from outside to the nucleus. Certain mutations in ras genes can permanently activate Ras, which can result in the incorrect propagation of intracellular signals. Such disregulated Ras signaling can ultimately lead to tumor growth and metastasis. Indeed, approximately 30% of all human tumors contain activating mutations in Ras. In pancreatic cancer this figure goes up to 95% followed by 55% in thyroid cancer.  In this research proposal we hope to gain deeper insights into the mechanism of Ras-mediated signal transduction by using a technique called high-resolution nuclear magnetic resonance (NMR) spectroscopy. With this technique we can now measure the biological activity of Ras and its oncogenic mutants more accurately.  We will seek an innovative way to attenuate the hyperactivity of mutant Ras based on our detailed biochemical and structural analysis of the Ras signaling.