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Re-engineering the spindle checkpoint response in fission yeastr

  • Full or part time
    Prof K Hardwick
  • Application Deadline
    Thursday, December 13, 2018
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Background: We study mitosis and chromosome segregation in yeast, with a particular focus on the spindle checkpoint. This cell cycle control monitors interactions between chromosomes and the mitotic spindle and delays mitotic progression until all pairs of sister chromatids are attached appropriately to spindle microtubules (1). We employ synthetic biology approaches to analyse this signalling pathway, and have now successfully generated a ‘wait anaphase’ signal entirely independently of kinetochores in fission yeast (2). This requires tethering of Mps1 kinase to one of its key substrates (3), thereby producing an active signalling scaffold that is sufficient to generate a prolonged metaphase arrest.

In this project you will employ a combination of synthetic biology, yeast genetics, biochemical purification, mass spectrometry and live-cell imaging to further characterise and gain control of this highly conserved checkpoint pathway. In particular you will dissect how yeast cells turn off their spindle checkpoint response. We have identified a number of candidate checkpoint silencing factors in a genome wide genetic screen. In addition, we identified several candidate regulators of PP1Dis2 through proteomic analyses of this key mitotic phosphatase. You will study the role of one or more silencing factors in detail. This project provides an excellent training opportunity, due to the breadth of approaches being employed in the fission yeast model system.

Lab web site: http://hardwick.bio.ed.ac.uk/

Funding Notes

The “Apply online” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.

If you would like us to consider you for one of our scholarships you must apply by 12 noon on 13 December 2018 at the latest.

References

(1) London, N. and Biggins, S. (2014). Signalling dynamics in the spindle checkpoint response. Nature Reviews Mol Cell Biology, 15, 736-747.

(2) Yuan, I., Leontiou, I., Amin, P., May, K.M., Chafraidh, S.S., Zlamalova, E. and Hardwick, K.G. (2017). Generation of a spindle checkpoint arrest from synthetic signalling assemblies. Current Biology 27, 137-143.

(3) Shepperd, L.A., et al. (2012). Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Current Biology, 22, 891-899.


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

FTE Category A staff submitted: 109.70

Research output data provided by the Research Excellence Framework (REF)

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