The molecular basis of regulating branched microtubule nucleation. BBSRC SWBio DTP PhD studentship 2025 Entry Ref: 5338

Supervisors

Lead Supervisor

Professor James Wakefield

Additional Supervisors

Dr Bertram Daum

Dr Vicki Gold

Dr Jonathan Phillips

Dr Misha Isupov

Location:  Streatham Campus, University of Exeter, Exeter, Devon

Up to 34 fully-funded 4-year PhD studentships* available to start in September 2025, across a wide range of bioscience disciplines.

To view projects available, and how to apply, visit the SWBio DTP website.

* Subject to meeting eligibility requirements. 

The award:

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). 

About:

The BBSRC-funded SWBio DTP involves a partnership of world-renown universities, research institutes and industry, based mainly across the South West and Wales.

This partnership has established international, national and regional scientific networks, and widely recognised research excellence and facilities.

We aim to provide you with outstanding interdisciplinary bioscience research training, underpinned by transformative technologies.

Programme Overview:

You will be recruited to a broad, interdisciplinary project, supported by a multidisciplinary supervisory team, with many cross-institutional projects available. There are also opportunities to:

• apply your research in an industrial setting (DTP CASE studentships).

• undertake research jointly with our core and associate partners (Standard DTP studentships with an associate partner).

• work with other national/international researchers.

• undertake fieldwork.

Our structured training programme will ensure you are well equipped as a bioscience researcher, supporting careers into academia, industry and beyond. 

First year

We provide a broad awareness of the fundamental research approaches in life sciences and how they could be applied to real-life situations through:

• two rotation projects - both allied with but in different disciplinary areas related to the PhD project.
• three taught units - training in Statistics, Bioinformatics, coding, experimental design, innovation and understanding the impact of your research.

Of note: You will need to successfully complete the first year to progress into your second year of studies.  Also, if you are unable to continue your PhD, an MRes exit route is available upon successful completion of the first year.

Second to fourth years

The remaining years will be more like a conventional PhD, where you will focus on your PhD project.

Project Description

"Mitosis, the accurate alignment and segregation of duplicated chromosomes is an essential cellular process that, when perturbed, contributes to diseases including cancer. Branched microtubule (MT) nucleation plays a vital role in mitosis, generating the bulk of the mitotic spindle. We have been working on two key protein complexes involved in this process, Augmin and the gamma-tubulin ring complex (gamma-TuRC). We hypothesize that when Augmin binds to the gamma-TuRC, it induces a structural alteration that enhances the probability of lateral interactions occurring between adjacent tubulin dimers. This, in turn, promotes the initiation of MT nucleation through the gamma-TuRC. 

In this project, you will test this hypothesis by elucidating the structures of the gamma-TuRC and Augmin, isolated from Drosophila (fruit fly) embryos, using cryo-electron microscopy (cryo-EM). The protein complexes will be isolated using a straight-forward, one-step biochemical purification procedure called cleavable-affinity purification (cl-AP), pioneered in our lab1,2. The samples will then be screened by conventional room-temperature transmission electron microscopy (TEM). This will reveal if the gamma-TuRC/Augmin purification is of sufficient concentration, purity and homogeneity for data acquisition or if the purification protocol needs to be improved. Once optimal gamma-TuRC/Augmin samples have been obtained, they will be prepared for cryo electron microscopy (cryoEM). Thousands of high magnification images of gamma-TuRC/Augmin will be recorded, and high-resolution 3D maps will be generated. The atomic model of g-TuRC/Augmin will be built into the cryoEM map, guided by other research in the lab, including cross-linking and HDX-mass spec data and AI-guided protein structure modelling software. This work will provide testable hypotheses as to the structural consequences of Augmin upon the gamma-TuRC. It will allow the design of modified Augmin or gamma-TuRC subunits that will be reintroduced into the Drosophila embryo, with the aim of activating or suppression branched MT nucleation.

This PhD project is an opportunity for an ambitious and interdisciplinary scientist to join our team of researchers. The student will be supported and assisted by other members of the Wakefield and Daum groups, including cell biologists, protein engineers and cryo-EM experts. The student will learn structural techniques, Drosophila cultivation, biochemistry, plus familiarization with several programming languages, mathematical modelling and statistical skills.

The Living Systems Institute is an interdisciplinary home for agile researchers across traditional disciplines. It brings together mathematicians, physicists, cell and molecular biologists, biomedical scientists and engineers. The student will thus be equipped with a rare and highly transferrable set of skills in both structural mass spectrometry of proteins and in vivo cell biology."

Funding and eligibility

Information about funding and eligibility >>

A limited number of funded-studentships are available for international students.

Supporting Equality, Diversity and Inclusion (EDI)

We support inclusive and flexible work environments, and welcome applications from all backgrounds and communities.

Our SWBio DTP EDI statement >>

How we support our diverse student cohort >>

PhD study adjustments and support >>

DTP virtual support events

We have events available to help you with deciding on a bioscience PhD, and support with applications and interviews.

Further information >>

Entry requirements

Academic criteria

Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant research or non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, quantitative/mathematical experience is needed.  This can be demonstrated through one or more of the following:

• Undertaking units as part of your degree that have a significant quantitative/mathematical component*
• Maths or Physics A-level (grade B and above)

*Significant mathematical component examples include; maths, statistics, bioinformatics.

Applicants must ensure they highlight their quantitative/mathematical background within their application and to upload any supporting evidence.

To support accessibility to PhD training opportunities, these studentships are only available to applicants that have not previously obtained or about to obtain a PhD degree (or equivalent).

Language requirements

If your first language is not English, you will need to meet the minimum English requirements for the programme.  Further information about these English requirements >>

We ask that the language requirements are met by 1st June at the latest, to allow adequate time to obtain any necessary documentation to allow you to study in the UK.  Further information about documentation required >>

How to apply

Apply now

Please be aware you will be asked to upload the following documents:

• CV
• Letter of application outlining your academic interests, prior research experience and reasons for wishing to undertake the project.  Please indicate your preferred project choice if applying for multiple BBSRC SWBio DTP projects.
• Personal Statement
• Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim transcript if you are still studying.
• Two academic referees - see information below about references.
• If you are not a national of a majority English-speaking country you will need to submit evidence of your proficiency in English (see entry requirements above)

The closing date for applications is midnight on Monday, 11 December 2024. 

Interviews will be held between 3-14 February 2025.

Reference Information

You will be asked to submit two references as part of the application process.  If you are not able to upload  your reference documents with your application please ensure you provide details of your referees.  If you provide contact details of referees only, we will not expect receipt of references until after the shortlisting stage. Your referees should not be from the prospective supervisory team.

If you are shortlisted for interview, please ensure that your two academic referees email their references to pgrapplicants@exeter.ac.uk, 7 days prior to the interview dates.  Please note that we will not be contacting referees to request references, you must arrange for them to be submitted to us by the deadline.

References should be submitted by your referees to us directly in the form of a letter. Referees must email their references to us from their institutional email accounts. We cannot accept references from personal/private email accounts, unless it is a scanned document on institutional headed paper and signed by the referee.

If you have any general enquiries about the application process please email pgrapplicants@exeter.ac.uk.

Project-specific queries should be directed to the primary supervisor.

Selection Process:

Information relating to the selection process can be found via the following link https://www.swbio.ac.uk/programme/selection-process/
Please note that nomination by a project supervisor therefore does not guarantee the award of a studentship.

Data Protection

During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

•     the selection panel and/or management board or equivalent of the relevant programme,
      which is likely to include staff from one or more other HEIs.
• administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.

Summary