Open Positions in the Schiebel Lab
|
Master Thesis Functional analysis of microtubule organization Centre for Molecular Biology (ZMBH) University of Heidelberg gamma-tubulin is a conserved member of the tubulin super-family that is involved in the formation of microtubules, the fibres that segregate the chromosomes in mitosis. gamma-tubulin assembles together with other proteins into larger complexes (1, 2). We were the first who discovered interactors of gamma-tubulin (3, 4) and who could show that gamma-tubulin complexes are recruited by receptors to the centrosome (5-7). The topic of the Master thesis is:
The student will use a broad method spectrum to study these open questions (expression of proteins in insect cells, protein purification, analysis of purified proteins by electron microscopy, molecular biology, in vivo mutant analysis, high resolution fluorescence microscopy, FRAP). Please send applications to Prof. Dr. Elmar Schiebel, ZMBH, University of Heidelberg, schiebel.elmar@zmbh.uni-heidelberg.de References: 1. A. Spang, S. Geissler, K. Grein, E. Schiebel, Journal of Cell Biology 134, 429 (1996). 2. G. Pereira, E. Schiebel, Science 302, 2120 (2003). 3. S. Geissler et al., Embo J 15, 3899 (1996). 4. M. Knop, G. Pereira, S. Geissler, K. Grein, E. Schiebel, Embo J 16, 1550 (1997). 5. M. Knop, E. Schiebel, Embo J 16, 6985 (1997). 6. M. Knop, E. Schiebel, Embo J 17, 3952 (1998). 7. G. Pereira, U. Grueneberg, M. Knop, E. Schiebel, Embo J 18, 4180 (1999).
|
||||
|
PhD or Postdoc position Centre for Molecular Biology (ZMBH) University of Heidelberg The function of Hippo pathway components at the human centrosome 1, 2 The Hippo pathway is a conserved signal transduction cascade that in mammals and Drosophila is best known for its function in organ size control 1, 3. Hippo pathway components (Rassf1, Mst1/2, WW45, Mob1 and Lats1/2) are tumour suppressors and their mis-regulation can cause tissue overgrowth. On the cellular level Hippo pathway components have functions in the regulation of cytokinesis, cell cycle progression, mitotic chromosome alignment and regulation of microtubule dynamics. Many Hippo pathway components are associated with the centrosome 4. However, the relevance of this interaction is unknown. Recently, we have identified Nek2 kinase as a protein that interacts with Hippo pathway components 2. Nek2 functions in chromosome disjunction at the beginning of mitosis 5. The goal of this project is therefore to understand how Hippo pathway regulation contributes to centrosome separation in a manner dependent on the cell cycle and on external stimuli. This will be addressed by biochemical approaches (LAP tag purification), siRNA studies, live cell imaging of cells with a defective Hippo pathway, and in vitro reconstitution of the Hippo-Nek2 pathway. We are looking for a highly motivated PhD student or postdoc with a strong background in biochemistry, cell biology or molecular biology. Successful candidates will be part of an international, highly motivated team of PhD students and postdocs that works at the forefront of scientific research (http://www.zmbh.uni-heidelberg.de/schiebel/default.shtml). The PhD student will be a member of the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS; http://www.hbigs.uni-heidelberg.de/). Please send written applications (CV, letter of motivation, transcripts) with 2-3 names of referees to Prof. Dr. Elmar Schiebel, ZMBH, Uni Heidelberg, schiebel.elmar@zmbh.uni-heidelberg.de. 1. Pan, D. Hippo signaling in organ size control. Genes Dev 21, 886-897 (2007). 2. Mardin, B. et al. Centrosome disjunction: a concerted action between Nek2A and components of the Hippo pathway. In revision (2009). 3. Zhao, B., Lei, Q. Y. & Guan, K. L. The Hippo-YAP pathway: new connections between regulation of organ size and cancer. Curr Opin Cell Biol 20, 638-46 (2008). 4. Guo, C. et al. RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr Biol 17, 700-5 (2007). 5. Fry, A. M., Meraldi, P. & Nigg, E. A. A centrosomal function for the human Nek2 protein kinase, a member of the NIMA family of cell cycle regulators. EMBO J 17, 470-81 (1998).
|
||||
|
PhD or Postdoc position Centre for Molecular Biology (ZMBH) University of Heidelberg The group of E. Schiebel at the ZMBH, University of Heidelberg has a long-lasting interest in the analysis of mitosis. The function and regulation of the mitotic spindle, which is the molecular machine that segregates the chromosomes, is the focus of our work. We use high-resolution microscopy, fluorescent recovery after photobleaching (FRAP), modeling and in vitro reconstitution assays to unravel essential principals of mitosis. Our group is optimally embedded into the live science campus of Heidelberg: we have close collaborations with groups from the German Cancer Research Centre (DKFZ; Dr. G. Pereira) and the European Molecular Biology Laboratory (EMBL; Drs. M. Knop, F. Nedelec and T. Surrey). Our work is important because malfunctions in mitosis contribute to the development of cancer and chemicals that inhibit structural and regulatory components of mitosis are used as anti-cancer drugs. We have an open PhD or postdoc positions: “Reconstitution of the mitotic spindle midzone”. The mitotic spindle is a dynamic machine that segregates the replicated chromosomes between the two daughter cells during cell division. In anaphase A shrinking kinetochore microtubules move the chromosomes towards the spindle poles. Concurrently, the spindle midzone is formed in the centre of the spindle by overlapping microtubules where microtubule-bundling proteins (Ase1), kinesin motor proteins (Cin8 and Kip1), chromosomal passenger proteins (separase-Slk19), +TIPs (Bim1/EB1, Stu1/CLASP, Bik1/CLIP-170, Stu2/XMAP215) and signaling molecules (Aurora B kinase) localize 1-4. The spindle midzone stabilizes the anaphase spindle in all eukaryotic cells by crosslinking microtubules of the two half spindles. It also drives spindle elongation in anaphase B and regulates cleavage furrow formation during cytokinesis in animal cells 5. The aim of this project (collaboration with Drs. T. Surrey and F. Nedelec, EMBL) is to reconstitute the spindle midzone with purified components, to measure biochemical properties of spindle midzone proteins by Total Internal Reflection Fluorescence (TIRF) microscopy (single molecule measurements) and FRAP. Findings will be verify in the cell system using cell and molecular biology. We are looking for highly motivated PhD student or postdoc with a strong background in biochemistry, cell biology or molecular biology. Successful candidates will be part of an international, highly motivated team of PhD students and postdocs that works at the forefront of scientific research (http://www.zmbh.uni-heidelberg.de/schiebel/default.shtml). The PhD student will be a member of the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS; http://www.hbigs.uni-heidelberg.de/). Please send written applications (CV, letter of motivation, transcripts) with 2-3 names of referees to Prof. Dr. Elmar Schiebel, ZMBH, Uni Heidelberg, schiebel.elmar@zmbh.uni-heidelberg.de. 1. Khmelinskii, A. & Schiebel, E. Assembling the spindle midzone in the right place at the right time. Cell Cycle 7, 283-286 (2008). 2. Khmelinskii, A., Lawrence, C., Roostalu, J. & Schiebel, E. Cdc14-regulated midzone assembly controls anaphase B. J Cell Biol 177, 981-993 (2007). 3. Khmelinskii, A., Roostalu, J., Roque, H., Antony, C. & Schiebel, E. Phosphorylation-dependent protein interactions at the spindle midzone mediate cell cycle regulation of spindle elongation. Dev Cell 17, 244-56 (2009). 4. Glotzer, M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol 10, 9-20 (2009). 5. Barr, F. A. & Gruneberg, U. Cytokinesis: placing and making the final cut. Cell 131, 847-60 (2007).
|
||||