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In vitro reconstitution of cooperative interactions at the kinetochore-microtubule interface


   School of Biological and Behavioural Sciences

  Dr Vladimir Volkov  Tuesday, January 31, 2023  Awaiting Funding Decision/Possible External Funding

About the Project

  • Supervisors: Dr Vladimir Volkov
  • Funding: China Scholarship Council (CSC)
  • Deadline: 31st January 2023

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological 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.

You will join the research group of Dr. Vladimir Volkov, newly established at the Biochemistry Department, and benefit from access to state of the art facilities for protein biochemistry, single-molecule and super-resolution fluorescence microscopy, and electron microscopy.

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.

To succeed in this project, you will have hands-on training in the relevant experimental methods. You will also have an opportunity to participate in scientific conferences in the UK and overseas.

Project description

Duiring cell division, eukaryotic cells must ensure proper attachments between chromosomes and the mitotic spindle to avoid the loss of genetic material, which can lead to aneuploidy, cancer, or cell death. These attachments are mediated by multiple copies of identical microtubule-binding protein complexes at the kinetochore interacting with microtubule ends. It is poorly understood how cooperative binding of these complexes to microtubules is regulated at molecular level. The project will make use of budding yeast as a simplified model system with only one microtubule per kinetochore, and well defined stoichiometry of the microtubule-binding proteins, such as the Ndc80 complex and the Dam1 complex.

In vitro reconstitution of an interaction between a microtubule end and recombinantly expressed kinetochore protein complexes will allow to dissect the self-assembly of microtubule end-binding oligomers, and the molecular interactions that hold them together, in a systematic manner. You will build on the unique methodologies established in the lab, including single-molecule fluorescence microscopy to assess the stoichiometry of microtubule-bound oligomers (1,4) , a DNA origami force sensor to study force coupling by these oligomers (2), and electron cryo-tomography to study the molecular interfaces involved in oligomerisation of microtubule end-bound protein complexes (3). 

More information about research in the Volkov group is available at http://www.vladimirvolkov.com

Eligibility and applying

Applicants must be:

- Chinese students with a strong academic background.

- Students holding a PR Chinese passport.

- Either be resident in China at the time of application or studying overseas.

- Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.

Please refer to the CSC website for full details on eligibility and conditions on the scholarship. 

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in an area relevant to the project, such as Biochemistry, Biophysics, Molecular Biology, or related disciplines. A masters degree is desirable, but not essential.

Prior experience with molecular cloning, protein engineering, or image analysis would give you an advantage.

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 Dr. Vladimir Volkov at . Formal applications must be submitted through our online form by 31st January 2023 for consideration, including a CV, personal statement and qualifications. 

Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CSC scholarship along with academic conditions still required to meet our entry requirements.

Once applicants have obtained their offer letter from Queen Mary they should then apply to CSC for the scholarship by the advertised deadline with the support of the project supervisor.

For September 2023 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2023. 

Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme. For further information, please go to: https://www.qmul.ac.uk/scholarships/items/china-scholarship-council-scholarships.html

Apply Online


Funding Notes

This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.

References

1. Polley S, Müschenborn H, Terbeck M, De Antoni A, Vetter IR, Dogterom M, Musacchio A#, Volkov VA#, Huis in ‘t Veld PJ#. Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding. bioRxiv (2022). doi: 10.1101/2022.08.25.505310
2. Nick Maleki A , Huis in 't Veld PJ, Akhmanova A, Dogterom M, Volkov VA#. Estimation of microtubule-generated forces using a DNA origami nanospring. J Cell Sci (2022) 136 (5), jcs260154. doi: 10.1242/jcs.260154
3. Maan R*, Reese L*, Volkov VA*, King MR, van der Sluis E, Andrea N, Evers W, Jakobi AJ, Dogterom M. Multivalent interactions facilitate motor-dependent protein accumulation at growing microtubule plus ends. Nature Cell Biology (2022), in press. doi: 10.1101/2021.09.14.460284
4. Volkov VA*, Huis in 't Veld PJ*, Dogterom M, Musacchio A. Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces. eLife (2018) 7, e36764. doi: 10.7554/eLife.36764
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