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EASTBIO Dissecting centromere identity and epigenetic inheritance

  • Full or part time
    Dr P. Heun
    Dr J Arulanandam
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

The centromere is a specialized chromatin region that is essential for proper segregation of mitotic chromosomes by forming a kinetochore. Centromere dysfunction results in aneuploidy or loss of chromosomes and is associated with cancer and miscarriage. In most eukaryotes centromeres are not encoded by DNA, but instead epigenetically defined by the histone H3-variant CENP-AcenH3 (dCENP-A/CID in flies). The molecular mechanisms by which CENP-A is deposited and how centromere identity is propagated through many cell divisions is still poorly understood. The simplicity of the Drosophila centromere makes it an ideal model to study CENP-A inheritance. In this project, we propose to reconstitute the dCENP-A deposition machinery (CAL1 and dCENP-C) bound to centromeric dCENP-A nucleosomes in vitro using recombinant proteins from E.Coli and baculovirus. Further insight into the structure of the dCENP-A machinery will be gained using X-ray crystallography and cryo electron microscopy in collaboration with the Jeyaprakash lab. The results obtained during this Ph.D. project will help understanding the molecular underpinnings of epigenetic propagation of centromere identity.

Funding Notes

The “Visit Website” button will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.

References

1. McKinley and Cheeseman IM, The molecular basis for centromere identity and function. Nat Rev Mol Cell Biol. 2016, 17:16-29 Review
2. Bobkov G, Gilbert N and Heun P, Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. J Cell Biol 2018, 217: 1957-1972
3. Roure V et al., Cell Reports, 2019

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

FTE Category A staff submitted: 109.70

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