Grant: Operating Grant

The Ras protein is a central regulator of cell proliferation and differentiation. Over 30% of all cancers in humans are associated with activating mutations in Ras. Therefore, elucidating the molecular consequences of Ras action will likely provide novel targets for therapeutic intervention against cancer. Ras governs proliferation and differentiation primarily by sending signals through the so-called MAPK pathway, which is composed of several individual proteins. The mechanisms and proteins required for Ras/MAPK function have been remarkably well conserved during evolution. Therefore, we use Drosophila fruit flies as a simpler tool to identify and characterize novel key proteins required for this pathway. Our work has thus far provided key insights with respect to the human Ras/MAPK pathway, some of which are currently being explored for anticancer therapeutic applications. Several basic questions regarding the inner workings of the Ras/MAPK pathway are still left unanswered and we propose here to tackle the most pressing ones using fruit flies as well as mammalian cell culture systems as experimental paradigms.