Haas, Gerald

ETH Zürich Gerald Haas Krek, Wilhelm HPL H 21.2 Schafmattstrasse 22 8093 Zuerich Phone: +41 44 633 21 15 E-Mail:

MY PROJECT

In multicellular organisms the availability of growth factors and nutrients provide signals and bioenergy to control cell growth, proliferation, metabolism and survival. In mammalian systems the balance between nutrient-rich cell survival and starvation induced apoptosis is tightly regulated by mitochondria. The mitochondria-based URI complex is a central integrator of survival signals,cell energy state and nutrient status. This multi-protein complex contains prefoldin chaperone family members like the unconventional prefoldin RPB5 interactor (URI), protein kinases, apoptosis effectors and phosphatases. This complex has been shown to integrate growth factors and nutrient signals via the mTOR/S6K pathway (Gstaiger, Luke et al. 2003). It has been demonstrated that in response to insulin – like growth factor (IGF) 1, S6 kinase 1 (S6K1) phosphorylates URI at S371 (Djouder, Metzler et al. 2007). Phosphorylation of URI leads to a dissociation of bound PP1y. Liberated PP1y has the ability to dephosphorylate S6K1 and possibly BAD andtherefore dampens S6K1 survival signalling. Based on this findings Djouder et. al proposed that activation of S6K1 activates a negative feedback cycle that keeps the balance between cell death and cell survival (Djouder, Metzler et al. 2007). On that basis, we try to elucidate glucose signaling mechanisms and adaptive changes in metabolism due to short-term low glucose availability.

I am a member of the Wilhelm Krek group.