“In vivo and in vitro analysis of molecular mechanisms of chromosome segregation”
Centre for Molecular Biology (ZMBH)
University of Heidelberg
The function and regulation of the mitotic spindle, which is the molecular machine that segregates the chromosomes, is one focus of our work. We use high-resolution microscopy, total internal reflection fluorescence (TIRF) microscopy, fluorescent recovery after photobleaching (FRAP), in vitro reconstitution assays and yeast genetics to unravel essential principals of chromosome segregation. Our group is optimally embedded into the life science campus of Heidelberg: we have close collaborations with groups from the German Cancer Research Centre (DKFZ; Dr. G. Pereira), the Center for Molecular Biology (ZMBH; Drs. S. Erhardt, O. Gruss and F. Melchior) and the Center of Organismal Studies (COS, Dr. J. Wittbrodt). This 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 position: “In vivo and in vitro analysis of molecular mechanisms of chromosome segregation”.
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 where the conserved microtubule-bundling protein 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 1-6. The spindle midzone stabilizes the anaphase spindle in all eukaryotic cells by crosslinking microtubules. It also drives spindle elongation in anaphase B and regulates cleavage furrow formation during cytokinesis in animal cells. The aim of this project is to study biochemical properties of spindle midzone proteins. Findings will be verified in the cell system using cell and molecular biology methods.
We are looking for a highly motivated PhD student with a strong background in biochemistry, cell biology or molecular biology. The successful candidate will be part of an international, highly motivated team of PhD students and postdocs that works at the forefront of scientific research. 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/).
The position is available from Oct. 2011-Sept. 2014.
Please apply to Prof. Elmar Schiebel, ZMBH, University of Heidelberg:
schiebel.elmar@zmbh.uni-heidelberg.de
Publications to this topic from the Schiebel group:
1 Pereira, G. & Schiebel, E. Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302, 2120-2124 (2003).
2 Khmelinskii, A. & Schiebel, E. Assembling the spindle midzone in the right place at the right time. Cell Cycle 7, 283-286 (2008).
3 Khmelinskii, A., Lawrence, C., Roostalu, J. & Schiebel, E. Cdc14-regulated midzone assembly controls anaphase B. J. Cell Biol. 177, 981-993 (2007).
4 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, 244-256 (2009).
5 Roostalu, J., Schiebel, E. & Khmelinskii, A. Cell cycle control of spindle elongation. Cell Cycle 9 (2010).
6 Roostalu, J. et al. Directional switching of the kinesin Cin8 through motor coupling. Science 332, 94-99 (2011).