Tracing ceramide and sphingolipid functions in model organisms
Ceramides and sphingolipids play crucial roles in cell physiology as demonstrated by the effects of mutations in their synthesis or modulation of the expression of key enzymes. However, we know little about the precise mechanism of their action. This project will use the tools of chemistry, genetics, cell biology, biochemistry and mass spectrometry to investigate the mechanism of ceramide and sphingolipid function. The project will include the synthesis of relevant sphingolipid precursors and analogs (such as photoactivatible analogs) as well as caged derivatives for delivery into cells through collaborations, the analysis of cells treated with these precursors and analogs by various techniques, including isolation of photocrosslinked targets and their identification by mass spectrometry. Lipid extraction and mass spectrometry will also be used to follow the fate of these precursors and analogs when added to cells.
1) Hannich, J.T., K. Umebayashi and H. Riezman (2011) Distribution and Functions of Sterols Sphingolipids. Cold Spring Harb.Perspect. Biol., ed. Kai Simons, Cold Spring Harbor Laboratory Press, pp 189-202.
2) Menuz, V., K. S. Howell, S. Gentina, S. Epstein, I. Riezman, M. Fornallaz-Mulhauser, M. O. Hengartner, M. Gomez, H.Riezman and J.-C. Martinou (2009) Protection of C. elegans from anoxia by HYL-2 ceramide synthase. Science 324, 381-384.
3) Guan, X, C.M. Souza, H. Pichler, G. Dewhurst, O. Schaad, K. Kajiwara , H. Wakabayashi, T. Ivanova, G. A. Castillon, M. Piccolis, F. Abe, R. Loewith, K. Funato, M. R. Wenk*, and H. Riezman* (2009) Functional Interactions between Sphingolipids and Sterols in Biological Membranes Regulating Cell Physiology. Mol. Biol. Cell, 20, 2083–2095.
4) Epstein, S., C.L. Kirkpatrick, G.A. Castillon, M. Muñiz, I. Riezman, F.P.A. David, C.B. Wollheim and H. Riezman (2012) Activation of the unfolded protein response pathway causes ceramide accumulation in yeast and INS-1E insulinoma cells. J. Lipid Res., doi: 10.1194/jlr.M022186
University of Geneva, Geneva, Switzerland
Supervisor: Howard Riezman
Howard Riezman is director of the Swiss National Centre of Competence in Research in Chemical Biology (www.nccr-chembio.ch). The institute is fully equipped for the latest techniques in chemical biology, biochemistry, microscopy and mass spectrometry. The association with the NCCR in Chemical Biology will provide exciting interactions with a local network of leaders in the Chemical Biology field.
• The candidate should have experience in chemistry and/or biochemistry. The project will involve work in both chemistry and biochemistry/cell biology so will provide an excellent interdisciplinary training.
• Proactive participation in SPHINGONET’s research & training program is expected through presentations and critical thinking at internal scientific forums, requiring excellent English presentation and writing skills. Strong communication skills and the ability to work in a team are a must.
• Candidates must fulfill the eligibility criteria for Marie Curie Initial Training Networks (FP7).
• Candidates should submit the complete application package.
• Suitable candidates will be invited for an interview by the supervisor of the project.
• PhD student for 3 years. Extension of the contract to 4 years is possible.
• Full-time (42 hours/week).