PhD position “Centrosome Duplication”

Centre for Molecular Biology (ZMBH) Heidelberg University

The group of E. Schiebel at the Center for Molecular Biology (ZMBH) (http://www.zmbh.uni-heidelberg.de/schiebel/default.shtml) at Heidelberg University, has a long-lasting interests in molecular mechanisms of cell cycle dependent centrosome duplication (for publications see below ^1-6).

We have an open PhD position: “Centrosome Duplication”.

Chromosomes become duplicated in S phase and are then segregated in mitosis by the mitotic spindle, a fascinating molecular machine that consists of microtubules, kinetochores and the two centrosomes. The centrosomes are large proteinaceous structures that organize microtubules and are associated with cell cycle regulators. Centrosomes, similar to DNA, duplicate just once during the cell cycle and overduplication causes cancer in human cells. Therefore, it is of uttermost importance to understand how centrosomes duplicate. Here, we are using budding yeast as a model organism. This work is important because malfunctions in mitosis contribute to the development of cancer and chemicals that inhibit structural and regulatory components of the mitotic spindle are used as anti-cancer drugs.

We use biochemistry, advanced microscopy (FRAP, FRET, photoactivation), electron microscopy and yeast genetics to unravel essential principals of centrosome duplication. The PhD student will have access to several high-end facilities at Heidelberg University.

We are looking for a highly motivated PhD student with a strong background in biochemistry. Successful candidates 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/) and the SFB 638. The E13/60% position is funded for 3 1/2 years.

The position is available from May 2012.

Please send applications to HBIGS (online application) or E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).

Selected publications of the Schiebel group:

1 Khmelinskii, A., Keller, P. J., Lorenz, H., Schiebel, E. & Knop, M. Segregation of yeast nuclear pores. Nature 466, (7305):E7301 (2010).

2 Pereira, G. & Schiebel, E. Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302, 2120-2124 (2003).

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, 244-256 (2009).

4 Mardin, B. R. et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat. Cell Biol. 12, 1166-1176 (2010).

5 Roostalu, J. et al. Directional switching of the kinesin Cin8 through motor coupling. Science 332, 94-99 (2011).

6 Kupke, T. et al. Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J 16, 3337-3352 (2011).

PhD position “Chromosome Segregation”

Centre for Molecular Biology (ZMBH) Heidelberg University

and The Paterson Institute for Cancer Research (PICR)

The groups of E. Schiebel at the Center for Molecular Biology (ZMBH) (http://www.zmbh.uni-heidelberg.de/schiebel/default.shtml), Heidelberg University, Germany and I. Hagan at the Paterson Institute, University of Manchester, UK (http://www.paterson.man.ac.uk/Research/groups.aspx?id=5) have long-lasting interests in the molecular analysis of chromosome segregation in mitosis (for publications see below ^1-13).

We have an open PhD position: “Chromosome Segregation”.

Chromosomes become duplicated in S phase and are then segregated in mitosis by the mitotic spindle, a fascinating molecular machine that consists of the microtubules, the kinetochores and the centrosomes. The centrosomes are large proteinaceous structures that organize microtubules and are associated with cell cycle regulators. Centrosomes similar to DNA duplicate just once during the cell cycle and overduplication causes cancer in human cells. Therefore, it is of uttermost importance to understand the regulation of centrosome duplication. Here, we use budding and fission yeast as model organisms to study centrosome duplication. This work is important because malfunctions in mitosis contribute to the development of cancer and chemicals that inhibit structural and regulatory components of the mitotic spindle are used as anti-cancer drugs.

We use biochemistry, advanced microscopy (FRAP, FRET, photoactivation), electron microscopy and yeast genetics to unravel essential principals of centrosome duplication. The PhD student will have access to several high-end facilities at Heidelberg University and The Paterson Institute.

We are looking for a highly motivated PhD student 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. 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/) and the GRK1188 (http://bzh.db-engine.de/default.asp?lfn=en4036). The PhD student will spend time in Heidelberg and Manchester to work at both institutions. An additional salary is paid during the time the PhD student is in Manchester to cover the costs of this visit. The PhD position is available from April 2012.

Please send applications to HBIGS (online application) or E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).

Selected publications of the Hagan and Schiebel groups:

1 Khmelinskii, A., Keller, P. J., Lorenz, H., Schiebel, E. & Knop, M. Segregation of yeast nuclear pores. Nature 466, (7305):E7301 (2010).

2 Pereira, G. & Schiebel, E. Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302, 2120-2124 (2003).

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, 244-256 (2009).

4 Mardin, B. R. et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat. Cell Biol. 12, 1166-1176, doi:ncb2120 [pii]10.1038/ncb2120 (2010).

5 Roostalu, J. et al. Directional switching of the kinesin Cin8 through motor coupling. Science 332, 94-99, doi:science.1199945 [pii]10.1126/science.1199945 (2011).

6 Kupke, T. et al. Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J 16, 3337-3352, doi:emboj2011242 [pii]10.1038/emboj.2011.242 (2011).

7 Grallert, A. et al. S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner. Genes Dev. 20, 2421-2436, doi:20/17/2421 [pii]10.1101/gad.381306 (2006).

8 Grallert, A. & Hagan, I. M. Schizosaccharomyces pombe NIMA-related kinase, Fin1, regulates spindle formation and an affinity of Polo for the SPB. EMBO J 21, 3096-3107 (2002).

9 Grallert, A., Krapp, A., Bagley, S., Simanis, V. & Hagan, I. M. Recruitment of NIMA kinase shows that maturation of the S. pombe spindle-pole body occurs over consecutive cell cycles and reveals a role for NIMA in modulating SIN activity. Genes Dev. 18, 1007-1021 (2004).

10 Petersen, J. & Hagan, I. M. Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast. Nature 435, 507-512, doi:nature03590 [pii]10.1038/nature03590 (2005).

11 Tamm, T. et al. Brr6 drives the Schizosaccharomyces pombe spindle pole body nuclear envelope insertion/extrusion cycle. J. Cell Biol. 195, 467-484, doi:jcb.201106076 [pii]10.1083/jcb.201106076 (2011).

12 Tallada, V. A., Tanaka, K., Yanagida, M. & Hagan, I. M. The S. pombe mitotic regulator Cut12 promotes spindle pole body activation and integration into the nuclear envelope. J. Cell Biol. 185, 875-888, doi:jcb.200812108 [pii]10.1083/jcb.200812108 (2009).

13 Alvarez-Tabares, I., Grallert, A., Ortiz, J. M. & Hagan, I. M. Schizosaccharomyces pombe protein phosphatase 1 in mitosis, endocytosis and a partnership with Wsh3/Tea4 to control polarised growth. J. Cell Sci. 120, 3589-3601, doi:jcs.007567 [pii]10.1242/jcs.007567 (2007).

PhD position:

 “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: “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 April 2012.

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).