Dissecting the self-interaction interfaces within oligomers of human kinetochore proteins binding to microtubule ends

• Supervisors Dr Vladimir Volkov
• Funding: SBBS Start-up Studentship
• Deadline: 28th February 2023

The following fully-funded PhD studentship is available in the School of Biological and Behavioural Sciences with an expected start date of Sept 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.

Within the Biochemistry Department, you will interact with researchers within several groups working on cell division and cell cycle, and a diverse range of other topics. To succeed in this project, you will have hands-on training in the relevant experimental and analytical methods. You will also have an opportunity to participate in scientific conferences in the UK and overseas.

Project description

Proper inheritance of genetic material relies on concerted action of kinetochore proteins firmly attaching the chromosomes to the microtubules of mitotic spindles. Microtubule-binding proteins are recruited to human kinetochores in hundreds of copies in a cooperative manner. However, the molecular interactions that mediate and regulate the homotypic interactions within the oligomers of similar protein molecules are poorly understood. 

We have recently characterised the loop region of the human Ndc80 complex as an interaction interface between neighbouring Ndc80 complexes bound to microtubules [1]. However, previous publications and our preliminary observations point towards multiple additional interfaces for attractive and repulsive self-interactions. The aim of this project is to dissect specific interactions within the folded and disordered regions of human kinetochore proteins and their contribution towards self-assembly of microtubule end-tracking and force-transmitting oligomers. 

We have previously developed approaches to reconstitute homo- and heterotypic interactions of multivalent microtubule end-binding complexes in vitro, and to study them using methods of single-molecule fluorescence microscopy [2] and electron cryo-tomography [3]. We have also developed a DNA origami force sensor to monitor the oligomerisation status of microtubule end-binding proteins during the transmission of force [4]. You will use protein engineering to produce recombinant microtubule end-binding proteins and their fragments, and unique methods established in the lab to interrogate performance of these proteins in functional assays. You will also use and/or develop custom image analysis and image processing scripts to extract quantitative information from microscopy data.

For more information about research in the group, please visit Dr. Volkov’s page at the QMUL website: https://www.qmul.ac.uk/sbbs/staff/vladimir-volkov.html

Funding

The studentship is funded by Queen Mary and will cover home tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the UKRI rate (£19,668 in 2022/23).

For international students interested in applying, please note that this studentship only covers home tuition fees and students will need to cover the difference in fees between the home and overseas basic rate. Tuition fee rates for 2023-24 are to be confirmed. Details on current (2022-23) tuition fee rates can be found at: https://www.qmul.ac.uk/postgraduate/research/funding_phd/tuition-fees/ 

Eligibility and applying

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, cell biology, biophysics, etc. A masters degree is desirable, but not essential.

Prior experience in protein biochemistry, molecular cloning, or microscopy will 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 [Email Address Removed]. Formal applications must be submitted through our online form by 28th February 2023.

The School of Biological and Behavioural Sciences is committed to promoting diversity in science; we have been awarded an Athena Swan Silver Award. We positively welcome applications from underrepresented groups.

http://hr.qmul.ac.uk/equality/ 

https://www.qmul.ac.uk/sbbs/about-us/athenaswan/ 

Apply Online