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Building the master controller of proliferation: Assembly of mTOR complexes

Research Project
 | 
01.09.2020
 - 31.08.2022

The protein kinase mammalian target of rapamycin (mTOR) is the master regulator of eukaryotic cell growth and proliferation. It exerts its functions via two different multiprotein complexes, which integrate cellular growth-factor signaling, nutrient availability and stress to control the switch between catabolism and anabolism, proliferation and survival. mTOR is the founding member of the PI3K-related kinase (PIKK) family, which includes five other structurally and functionally diverse kinases linked to central DNA and RNA quality control systems. Despite emerging insights into signaling events of mTOR and other PIKKs, the assembly of their active complexes through a conserved chaperone system remains poorly characterized. My PhD project aims at the characterization of mTOR (and PIKK) folding and complex assembly and its implications in eukaryotic cellular signaling in health and disease. The specific recognition of mTOR by its chaperone complex will be examined primarily through cryo-electron microscopy in combination with biophysical studies. Biochemical in vitro and cellular experiments will provide crucial insights into the mechanism of PIKK folding, complex assembly and release from the assembly machinery. Links between mechanisms of mTOR complex assembly and human disease will be investigated via multi-omics data and potentially provide novel therapeutic approaches.

Funding

Building the master controller of proliferation: Assembly of mTOR complexes

Foundations / Associations (GrantsTool), 09.2020-08.2022 (24)
PI : Maier, Timm.
CI : Berneiser, Karolin.

Members (2)

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Timm Maier

Principal Investigator
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Karolin Berneiser

Co-Investigator