Organization
Prof. Bernard C. Rossier
rossier@jeantet.ch

Secretariat:
Ms Marie-Madeleine
Cuenat
+41 22 704 36 41
cuenat@jeantet.ch

Webmaster: morard@jeantet.ch

Louis-Jeantet
Foundation
Chemin Rieu 17
P.O. Box 270
1211 Geneva 17
Switerland
Phone
+41 22 704 36 36
Fax
+41 22 704 36 37


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Robbie Loewith

Faculty of Science, University of Geneva (Switzerland)

Wednesday, October 24, 08:30 - 09:00

Chemical and genetic interrogations of TOR signalling in yeast

The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that regulates many aspects of eukaryote physiology and metabolism. TOR proteins operate in two distinct multiprotein complexes known as TOR Complex 1 and TOR Complex 2, and, like TOR, these complexes are widely conserved.  TORC1 and TORC2 are independently regulated downstream of environmental as well as cell-intrinsic cues, and, in turn, each complex independently regulates distinct aspects of eukaryote growth.

Owing to its sensitivity to the macrolide rapamycin, the pathways up- and downstream of TORC1 are relatively well understood; in contrast, it has been much more challenging to elucidate the pathways in which rapamycin-insensitive TORC2 operates. The recent development of small-molecules, ATP-competitive TOR-inhibitors which inhibit both TOR complexes have greatly facilitated the study of TORC2 and, surprisingly, of TORC1. Unfortunately, these “next generation” TOR inhibitors are not amenable for use in the genetically malleable model eukaryote Saccharomyces cerevisiae. To help us probe TOR function in yeast we have sought out novel TOR-inhibitors. 

These yeast-permeative inhibitors, along with chemical-genetic and quantitative mass spectroscopy approaches have allowed us to ascribe new functions to TORC2 including a central, conserved role in plasma membrane homeostasis. The plasma membrane is composed of various domains of distinct composition and, as it delimits the cell, its integrity is essential for cell survival.  In collaboration with the group of Tobias Walther, we found that membrane domains function to couple changes in plasma membrane tension to TORC2:  tension activates TORC2 signalling resulting in increased production of sphingo- and other lipids, and ultimately in restoration of plasma membrane homeostasis.

 

Biography

Robbie Loewith grew up on a dairy farm near Hamilton, Ontario, Canada.  He obtained his BSc in 1994 at the University of Guelph (Ontario) and his PhD in 2000 under the supervision of Prof. Dallan Young at the University of Calgary (Alberta).  He then moved to Basel (Switzerland) to pursue post doctoral studies under the mentorship of Prof. Michael N. Hall at the Biozentrum.  During this time he became interested in understanding how TOR proteins regulate diverse aspects of eukaryote physiology.  Continuing in this vein, in 2005 he started an independent research group in the Department of Molecular Biology at the University of Geneva.  In 2006, he was granted a Professorship from the Swiss National Science Foundation, and in 2011, he was granted tenure as an Associate Professor.

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Website Department of Molecular Biology

Website Swiss National Centre of Competence in Research, Frontiers in Genetics

Website Swiss National Centre of Competence in Research, Chemical Biology