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Dr. Elmar SchiebelSegregation of chromosomes in mitosis and regulation of mitotic exit

During mitosis and meiosis, the duplicated genetic information, the chromosomes, are separated by a precise machine, which is called the mitotic or meiotic spindle, to opposite spindle poles. After the subsequent cell division, each daughter cell has an identical chromosome set. Defects in this machine can lead to cancer or Down-Syndrom. Our work aims to understand how this machine works and is regulated. For this, we purify the protein components of the mitotic spindle and analyze their properties in the test tube. Using the new tools of genome editing (CRISPR-Cas9), we manipulate genes that code for mitotic spindle components in human tissue culture cells and monitor the defects by microscopy. In collaboration with chemists and structural biologists, we develop drugs that impair this machine specifically in dividing cancer cells.

Current Research

During mitosis and meiosis, the duplicated genetic information, the chromosomes, are separated by a precise machine, which is called the mitotic or meiotic spindle, to opposite spindle poles. After the subsequent cell division, each daughter cell has an identical chromosome set. Defects in this machine can lead to cancer or Down-Syndrom. Our work aims to understand how this machine works and is regulated. For this, we purify the protein components of the mitotic spindle and analyze their properties in the test tube. Using the new tools of genome editing (CRISPR-Cas9), we manipulate genes that code for mitotic spindle components in human tissue culture cells and monitor the defects by microscopy. In collaboration with chemists and structural biologists, we develop drugs that impair this machine specifically in dividing cancer cells.

5 Selected publications

Atorino, E.S., S. Hata, C. Funaya, A. Neuner, and E. Schiebel. (2020). CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion. Nat. Comm., Feb 14;11(1):903. doi: 10.1038/s41467-020-14767-2.

Liu, P., E. Zupa, A. Neuner, A. Böhler, J. Loerke, D. Flemming, T. Ruppert, T. Rudack, C. Peter, C. Spahn, O.J. Gruss, S. Pfeffer*, and E. Schiebel*. (2019). Insights into the assembly and activation of the microtubule nucleator gamma-TuRC. Nature, doi: 10.1038/s41586-019-1896-6. [Epub ahead of print]. * Co-corresponding authors.

Hata, S.*, A. Pastor Peidro, M. Panic, P. Liu, E. Atorino, C. Funaya, U. Jäkle, G. Pereira, and E. Schiebel*. (2019). Therbalance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly. Nat. Cell Biol., 21:1138-1151. * Co-corresponding authors.

Gunzelmann, J., D. Rüthnick, T.C. Lin, W. Zhang, A. Neuner, U. Jäkle, and E. Schiebel. (2018). The microtubule polymerase Stu2 promotes oligomerization of the gamma-TuSC for cytoplasmic microtubule nucleation. eLife, 2018 Sept 17;7. pii: e39932. doi: 10.7554/eLife.39932.

Vlijm, R., X. Li, M. Panic, D. Rüthnick, S. Hata, F. Herrmannsdörfer, T. Kuner, M. Heilemann, J. Engelhardt, S.W. Hell*, and E. Schiebel*. (2018). STED nanoscopy of the centrosome linker reveals a CEP68-organised, periodic rootletin network anchored to a C-Nap1 ring at centrioles. Proc. Nat. Acad. Sci. USA, 2018 Febr. 20. https://doi.org/10.1073/pnas.1716840115 [Epub ahead of print]. * Co-corresponding authors.