Birol Cabukusta

Name

Name: Birol Cabukusta
Nationality: Turkish

University of Osnabrueck,
Molecular Cell Biology,
Barbarastrasse 13,
49076 Osnabruck
Germany

Contact details:bcabukusta@uos.de

Biosketch

Birol Cabukusta lives in Osnabruck.

Project title: Control of mitochondrial apoptosis by a candidate ceramide sensor in the ER

(Targeting sphingolipid homeostatic machinery for modulating drug-induced apoptosis in tumors)

Project summary:

Cells routinely synthesize ceramides in the endoplasmic reticulum (ER) as precursors for sphingolipids to form an impermeable plasma membrane. As ceramides are engaged in apoptotic pathways, cells would need to monitor their levels closely to avoid killing themselves during sphingolipid biosynthesis.

We previously identified SMSr, an ER-resident ceramide phosphoethanolamine (CPE) synthase, as a key suppressor of ceramide-mediated cell death (Vacaru et al. 2009, Tafesse et al. submitted). Disrupting SMSr function causes a rise in ER ceramides and their flow in mitochondria, triggering a mitochondrial pathway of apoptosis. How SMSr regulates ER ceramides is unclear. SMSr contains a N-terminal sterile-alpha motif or SAM domain that mediates dimerization/oligomerization of the enzyme and bears striking similarity to the SAM domain of diacylglycerol kinase delta. While SAM is dispensable for SMSr-catalyzed CPE production, its removal suffices to trigger ceramide accumulation and cell death.

These results define ER ceramides as bona fide transducers of apoptosis and suggest a role of SMSr as ceramide sensor to protect cells against the inherent danger of sphingolipid biosynthesis. To further elucidate the mechanism by which SMSr controls ER ceramides, our ongoing work focuses on a proteome-wide search for SMSr binding partners and on the isolation and functional analysis of oligomerization-defective SMSr mutants.

Supervisors

Joost Holthuis (University of Osnabrueck, Germany)
Christian Heinis (EPFL, Lausanne, Switzerland)

Biosketch 1st scientific supervisor:

Joost Holthuis studied biology at Utrecht University, NL, and graduated with honors on neuroendocrine secretion in 1996 at the Radboud University Nijmegen, NL. Following postdoctoral studies on syntaxins with Hugh Pelham at the MRC Laboratory of Molecular Biology in Cambridge, UK, he returned to the NL to start his own group at the Academic Medical Center in Amsterdam. In 2001 his group moved to the Bijvoet Center and Institute of Biomembranes at Utrecht University, where he worked as associate professor. In 2012 he accepted a position as professor of Molecular Cell Biology at the University of Osnabrueck. Research in his group focuses on membrane lipid metabolism, transport and homeostasis; the underlying protein machinery of lipid converters, sensors and flippases; and how dysfunction of this machinery results in systemic failure and disease.