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Safe-guarding genome integrity during mammalian cell division

  • Full or part time
    Dr U Gruneberg
  • Application Deadline
    Friday, January 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The key goal of cell division is the correct segregation of the genetic material over multiple generations. Failure of this process can result in cell death or trigger tumorigenesis. An important prerequisite for correct chromosome segregation and maintenance of genomic integrity in eukaryotes is the tight attachment of the chromosomes to microtubules during cell division, making faithful partitioning of the chromosomes possible. The fidelity of this process is achieved through the actions of the spindle assembly checkpoint, a crucial molecular safe-guarding mechanism that monitors the formation of stable microtubule-kinetochore attachments. Our aim is to understand how this mechanism ensures accurate segregation of the chromosomes in mammalian cells, and what aspects of this process go wrong in cancer cells. We have recently discovered distinct roles for specific mitotic kinase-phosphatase modules in the regulation of chromosome segregation and the spindle assembly checkpoint, and will now aim to further understand their actions and interplay by using a combination of biochemical and cell biological techniques, including cutting edge fixed and live cell imaging, CRISPR/Cas9-mediated genetic manipulation of cell lines, in vitro protein assays, immunoprecipitations and mass spectrometry.

Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.

References

1. Hayward, D., Alfonso-Perez, T., and Gruneberg, U. (2019). Orchestration of the spindle assembly checkpoint by CDK1-cyclin B1. FEBS Lett. 10.1002/1873-3468.13591.

2. Hayward, D., Bancroft, J., Mangat, D., Alfonso-Perez, T., Dugdale, S., McCarthy, J., Barr, F.A., and Gruneberg, U. (2019). Checkpoint signalling and error correction require regulation of the MPS1 T-loop by PP2A-B56. J Cell Biol 218. 10.1083/jcb.201905026.

3. Alfonso-Perez, T., Hayward, D., Holder, J., Gruneberg, U., and Barr, F.A. (2019). MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling. J Cell Biol 218, 1108-1117. 10.1083/jcb.201808015. PMC6446853

4. Hayward, D., Alfonso-Perez, T., Cundell, M.J., Hopkins, M., Holder, J., Bancroft, J., Hutter, L.H., Novak, B., Barr, F.A., and Gruneberg, U. (2019). CDK1-CCNB1 creates a spindle checkpoint-permissive state by enabling MPS1 kinetochore localization. J Cell Biol 218, 1182-1199. 10.1083/jcb.201808014. PMC6446832

How good is research at University of Oxford in Biological Sciences?

FTE Category A staff submitted: 223.80

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