Extracellular Matrix Adhesion and Cell Cycle Progression

Applications are invited for a three-year PhD studentship. The studentship will start on 1 October 2022.

Apply

To apply please use the online application form. Simply search for PhD Medical Studies (and select the entry point of October 2022), then clearly state that you are applying for a PhD studentship and name the project at the top of your personal statement.

Online application

Before applying, please ensure you have read the Doctoral College’s general information on applying for a research degree.

For more information on the admissions process, please contact doctoralcollege@plymouth.ac.uk.

Project description

For most cells, cell cycle progression is anchorage dependent, requiring cell–extracellular matrix (ECM) interactions via integrin receptors and signalling downstream of actin-associated adhesion complexes. Before entry into mitosis, adhesion complexes are rapidly disassembled, and cells retract from their surroundings and round up to divide, suggesting that the cell-cycle machinery is able to regulate integrin ECM adhesion complexes.

We have recently demonstrated that, as cells progress through S phase, adhesion complex area increases alongside the formation of robust actin stress fibres. Subsequently, adhesion complex area decreases and stress fibres disassemble when cells enter G2. These changes in adhesion complexes and the cytoskeleton are primarily mediated by the master cell-cycle regulator CDK1, via a direct interaction with the adhesion protein talin. Preventing the reduction in adhesion complexes observed in G2 leads to fewer cells entering mitosis and aberrant cell division, highlighting that these changes in adhesion and the cytoskeleton are key events that occur in G2 in preparation for entry into mitosis. However, the mechanisms by which CDK1 promotes S-phase adhesion growth are unknown.

The successful candidate for this PhD studentship will utilise cutting edge microscopy techniques, flow cytometry, proteomic approaches and Western blotting to determine how the reciprocal relationship between ECM adhesion and cell-cycle progression is regulated. This will be focused around the mechanisms by which CDK1 promotes adhesion growth in S-phase, and the consequences of this on the S-G2 transition. Furthermore, how changes in ECM composition and rigidity are able to influence cell-cycle progression will also be investigated.

Eligibility

Applicants should have a first or upper second class honours degree in an appropriate subject and preferably a relevant Masters qualification.

The studentship is supported for three years and includes full home tuition fees plus a stipend of £16,062 per annum (2022/23 rate). The studentship will only fully fund those applicants who are eligible for home fees with relevant qualifications. Applicants normally required to cover international fees will have to cover the difference between the home and the international tuition fee rates (approximately £12,670 per annum).

NB: The studentship is supported for three years of the four-year registration period. The fourth year is a self-funded ‘writing-up’ year.

If you wish to discuss this project further informally, please contact Dr Matt Jones.

The closing date for applications is 12 noon on 8 July 2022. Shortlisted candidates will be invited for interview on 25 July. We regret that we may not be able to respond to all applications. Applicants who have not received a response within six weeks of the closing date should consider their application has been unsuccessful on this occasion.