Open Positions in the Schiebel Lab

Bachelor/Master Thesis “How to regulate the duration of mitosis and control cell fate decisions”
Every day, millions of cells undergo mitosis in our bodies to support growth and replace damaged cells. Therefore, numerous safeguards have evolved to ensure that genomic stability is maintained. Recent findings support that time spent in mitosis is measured and can affect cell fate decisions, if mitotic timing is abnormally extended. However, it is still not clear how cells are able to monitor mitotic duration and translate this into cell fate decisions. Recent findings have proposed pathways that can monitor mitotic length and lead to a p53-mediated arrest if a timing threshold is surpassed, even in the absence of DNA damage. This mechanism can prevent repeated damaged cells from proliferating and prevent cycles of chromosomal instability. Recent findings in the Schiebel lab identified that upon prolonged mitosis the protein kinase HIPK2, a known p53 activator, could indirectly influence Cyclin B1 levels to further maintain mitotic arrest. Except for HIPK2, CDC14B is also involved in the regulation of Cyclin B1 and the overall progression of mitosis. CDC14 is a phosphatase that has been widely studied in Saccharomyces cerevisiae (ScCDC14) for its central role in mitotic exit and cytokinesis. But its role in human cells is largely understudied.

In this project, we aim to investigate the role of HIPK2 and CDC14B in mitosis and mitotic arrest, and explore novel interactors of these proteins. We believe that understanding this mechanism, which plays an important part in preventing cancerous cells from spreading, could improve detection and therapy of cancer.
Please send application with CV and a short statement of interests to Prof. Elmar Schiebel at schiebel.elmar@zmbh.uni-heidelberg.de

Techniques that will be used in this project:
- Maintaining cell lines, transfection, and transduction
- CRISPR/Cas9 genetic editing, and Molecular cloning
- Western blot, PCR
- Flow cytometry
- Microscopy

Relevant literature:

- Partscht, Patrick et al. “The HIPK2/CDC14B-MeCP2 axis enhances the spindle assembly checkpoint block by promoting cyclin B translation.” Science advances vol. 9,3 (2023): eadd6982. doi:10.1126/sciadv.add6982
- Partscht P, Schiebel E. The diverging role of CDC14B: from mitotic exit in yeast to cell fate control in humans. EMBO J. (2023);42(16):e114364. doi:10.15252/embj.2023114364
- Agustina P. Bertolin, Vanesa Gottifredi, A mitotic stopwatch determines cell fate. Science383,1414-1415(2024). DOI:10.1126/science.ado5703

Master Thesis “Centriole Duplication”

Are you passionate about cell biology and eager to explore the fascinating world of centrioles? The Prof. Elmar Schiebel at the Centre for Molecular Biology (ZMBH) at Heidelberg University invites applications for a Master position focusing on centriole duplication.

About the Position:
The successful candidate will join Prof. Elmar Schiebel’s research group, renowned for its work on gamma-tubulin, centrioles and centrosome function. This Master project will investigate the molecular mechanisms underlying centriole duplication. The research will combine advanced microscopy techniques, biochemistry, and genetic tools to unravel the complexities of centriole assembly and function. The Master student will be supported by a Hiwi contract of ca. 500 € per months.
How to Apply: Interested candidates should send their application, including a CV, cover letter, and contact information for two references, to Prof. Elmar Schiebel at schiebel.elmar@zmbh.uni-heidelberg.de.
Relevant recent publications:

1 Liu, P. et al. Insights into the assembly and activation of the microtubule nucleator gamma-TuRC. Nature 578, 467-471 (2020). https://doi.org:10.1038/s41586-019-1896-6
2 Würtz, M. et al. Modular assembly of the principal microtubule nucleator ?-TuRC. Nat Comm 473, doi: 10.1038/s41467-41022-28079-41460 (2022).
3 Karasu, O. R., Neuner, A., Atorino, E. S., Pereira, G. & Schiebel, E. The central scaffold protein CEP350 coordinates centriole length, stability, and maturation. J Cell Biol 221 (2022). https://doi.org:10.1083/jcb.202203081
4 Gao, Q. et al. The structure of the gamma-TuRC at the microtubule minus end - not just one solution. Bioessays, e2400117 (2024). https://doi.org:10.1002/bies.202400117
5 Vermeulen, B. J. et al. gamma-TuRC asymmetry induces local protofilament mismatch at the RanGTP-stimulated microtubule minus end. EMBO J (2024). https://doi.org:10.1038/s44318-024-00087-4 **************************