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Human chromosome segregation principles: Regulation of Astrin-PP1 interaction


Project Description

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

Aggressive cancers contain cells that display irregular number of chromosomes - a state called aneuploidy. Aneuploidy can directly arise from errors in the process of chromosome segregation that can lead to the gain or loss of chromosomes in the daughter cells. The precise molecular lesions that cause aneuploidy in cancers has remained elusive. The Draviam group is interested in identifying these aneuploidy promoting lesions and in understanding the immediate and long-term impact of these lesions. When human cells undergo division, microtubules capture and segregate chromosomes into two equal sets. Chromosome-microtubule attachment is mediated by a large macromolecular structure - the Kinetochore (KT) - made of more than 100 proteins. Proper KT assembly and function are essential for the accurate segregation of chromosomes. We showed that KTs attached to microtubule -ends, but not -walls, recruit a 4-member Astrin-SKAP complex, which stabilises KT-MT attachment (Cur Bio 2013, Nature Comm 2017). With the Pickersgill and Martin-Duran labs, the Draviam lab showed that Astrin’s enrichment at the KT requires its interaction with PP1 phosphatase (eLife, 2019). Identifying why Astrin-PP1 interaction occurs only at KTs bound to MT-ends, and nowhere else in the cell, can reveal how cells monitor KT-MT attachment. To address this question, the student will use a combination of molecular and cell biology and structural biology tools. By defining the structural and molecular basis for Astrin-PP1 interaction the student will uncover how cells monitor chromosome-microtubule attachment status and prevent aneuploidy.

For additional information on the research project, the applicant can write to

Eligibility

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree and a masters degree in an area relevant to the project (Cell or Molecular Biology). Masters degree is optional in cases where the student can show research experience in the areas of Cell Biology, Molecular Biology or Structural Biology.

The student should have some 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/

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 (£17,009 in 2019/20).

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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