Sphingolipid homeostatic machinery as target for modulating drug-induced apoptosis in tumors


Project description
Ceramide is intimately involved in the regulation of cancer-cell growth and survival, and many anti-cancer regimes cause an increase in de novo ceramide synthesis, leading to G0/G1 arrest and apoptosis. In view of the tumor suppressor activities of ceramide, this project will evaluate key mediators of ceramide homeostasis as targets for sensitizing cancer cells to chemotherapeutic drugs using overexpression and knock-down strategies. Inhibitory peptide reagents will be developed against proteins whose down-regulation sensitize cancer cells for drug-induced apoptosis. Because mistargeting of ER ceramides to mitochondria appears a key step in committing cells to death, chemical dimerizer approaches will be used to engineer switchable ceramide transfer proteins for manipulating the ceramide flow into mitochondria.

Further reading
Vacaru et al., 2009, J Cell Biol 185:1013-1027
Puts et al., 2010, J Proteome Res 9:833-842
Tafesse and Holthuis, 2010, Nature 463:1028-1029

Host institute
Universität Osnabrück (UOS), Germany
Molecular Cell Biology Division
Supervisor: Prof. Dr. Joost Holthuis
E-mail: holthuis@biologie.uni-osnabrueck.de
Phone: +49 541969 7140
Web: http://holthuis-lab-uos.de

The UOS is a young university located in the historical town of Osnabrück, the only German city situated in a national park (the ‘UNESCO Geo park TERRA.vita’). The newly established Molecular Cell Biology Division, led by Joost Holthuis, is embedded in the strongly interdisciplinary Collaborative Research Centre “Physiology and Dynamics of Cellular Microcompartments”, which comprises 14 research groups from the Universities of Osnabrück and Münster whose common focus is both thematically and methodologically linked to the current project. This Research Centre offers an outstanding scientific environment as well as direct access to state-of-the-art facilities in chemical biology, biophysics, proteomics, lipidomics, electron microscopy and live cell imaging.

•    We are looking for an ambitious and interactive individual with MSc degree in biochemistry, molecular cell biology or chemical biology. A solid background in assay development is an advantage. Prior experience with RNAi and/or lentivirus transduction of mammalian cells is an asset.
•    The candidate will be part of an international team of chemists, geneticists, biophysicists, biochemists and cancer biologists. Good communication skills are essential.
•    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. The ability to work in a team is 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).