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School of Biological and Behavioural Sciences

Single-molecule dissection of force-transmitting kinetochore-microtubule interface

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.

The Volkov lab aims to understand the molecular and structural mechanisms underlying force transmission and force sensing at the interface between the cytoskeleton and other components of the cell. You can find more information about the group at our website: www.volkovlab.com. The Thorpe lab are experts in genetics and cell biology of budding yeast.

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.

You will have access to state-of-the-art facilities for protein production, light and electron microscopy. To master unique single-molecule approaches that were previously developed in the Volkov lab, you will receive hands-on training from the PI and group members. Training for in vivo assays will be available through the collaboration with the Thorpe lab.

Opportunities are available to present your research findings at conferences in the UK and overseas. Additionally, you will receive support in preparing you for your next career step after the PhD.

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, and how microtubule detachment is prevented by the correctly attached kinetochore.

The project will make use of the budding yeast as a simplified model system with well defined stoichiometry of the microtubule-binding proteins, such as the Ndc80 complex and the Dam1 complex. You will use recombinant kinetochore complexes and single-molecule fluorescence microscopy to reconstitute kinetochore-microtubule interactions in vitro. Specifically, you will address the molecular requirements for the self-assembly of the functional microtubule-binding unit of the kinetochore, and its effects on the force transmission and the dynamics of the kinetochore-bound microtubule end.

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] , a single-molecule approaches to study force coupling by these oligomers [2], and electron microscopy to study the molecular interfaces involved in oligomerisation of microtubule end-bound protein complexes [3].

The interaction interfaces identified using these in vitro assays will be further studied in vivo in collaboration with the Thorpe lab.

Funding

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.

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 Biochemistry, Biophysics, or related disciplines, and a strong interest in single-molecule biophysics. A masters degree is desirable, but not essential.

Prior experience in molecular cloning, protein biochemistry, and/or microscopy will help you to quickly get up to speed with the project.

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 Vladimir Volkov at v.volkov@qmul.ac.uk 

Formal applications must be submitted through our online form by 31st January 2024 for consideration, including a CV, personal statement and qualifications. You must meet the IELTS/ English Language requirements for your course and submit all required documentation (including evidence of English Language) by 14th March 2024. You are therefore strongly advised to sit an approved English Language test as soon as possible. 

Shortlisted applicants will be invited for a formal interview by the supervisor. If you are successful in your application, then you will be issued an QMUL Offer Letter, conditional on securing a CSC scholarship along with academic conditions still required to meet our entry requirements. Once applicants have obtained their QMUL Offer Letter, they should then apply to CSC for the scholarship by in March 2024 with the support of the supervisor.

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

References

1. Polley et al., EMBO J (2023)
2. Nick Maleki et al., J Cell Sci (2023)
3. Maan*, Reese*, Volkov*, et al., Nat Cell Biol (2023)
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