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Human chromosome segregation principles: Regulation of Astrin-PP1 interaction


School of Biological & Chemical Sciences

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Prof Viji Draviam , Prof Richard Pickersgill , Dr Chema Martin No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Research Environment
The School of Biological and Chemical Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 160 PhD students working on projects in the biological, chemical and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services. The student will have access to a cutting-edge live-cell and super-resolution microscopy facility to study cell division process, and gain support from an in-house protein purification facility for Structural Biology studies.
Training and Development
Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career. The student will gain training in Cell, Molecular and Structural Biology techniques and Bioinformatics tools.
Project Details
Aneuploidy (irregular chromosome numbers) can promote aggressive cancer, premature ageing, infertility and multidrug resistance. The precise molecular lesions that drive aneuploidy in pathologies remain unclear. To address this, we need a clear molecular understanding of how microtubules capture and segregate chromosomes during the process of cell division.

Chromosome-microtubule attachment is facilitated by a large macromolecular complex, the kinetochore, made of over 100 evolutionarily conserved proteins. Proteins that stabilise kinetochore-microtubule attachment are crucial for the accurate segregation of chromosomes. We showed that human kinetochores attached to the very ends of microtubules, but not microtubule-walls, recruit a 4-member Astrin complex that is essential to stabilise kinetochore-microtubule attachment (Curr Bio 2013, Nature Comm 2017). More recently, we showed how the Astrin complex stabilises kinetochore-microtubule attachments by recruiting PP1, a phosphatase, near the evolutionarily conserved tetramerisation domain of the Ndc80 complex (eLife, 2019). The student will define the structural and molecular basis for Astrin-PP1 and Astrin-Ndc80 interactions using a combination of Structural Biology, Evolutionary Biology and Cell Biology tools. This multi-disciplinary study will shed light on why the Astrin complex is recruited selectively to kinetochores attached to microtubule-ends, and how the complex senses and stabilises correct attachment status. The findings will expand our fundamental understanding of how normal cells monitor chromosome-microtubule attachment status and prevent aneuploidy.
Eligibility
Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in Biological Sciences or a masters degree in an area relevant to the project (Biochemistry, Cell or Molecular Biology). Research experience in Biochemistry or Molecular Biology is essential.

The student should have demonstrable research experience in the form of research thesis or publications.

Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our English language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/

Informal enquiries about the project can be sent to [Email Address Removed]. Formal applications should be submitted through our online form by the stated deadline.

The School of Biological and Chemical Sciences is committed to promoting diversity in science; we have been awarded an Athena Swan Bronze Award. We positively welcome applications from underrepresented groups.
http://hr.qmul.ac.uk/equality/
https://www.qmul.ac.uk/sbcs/about-us/athenaswan/

Funding Notes

This studentship is open to applicants worldwide and is funded by a Queen Mary University of London Principal's Studentship. It will cover tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the Research Council rate (£17,285 in 2020/21).

References

Conti et al., 2019 Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation https://elifesciences.org/articles/49325
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