Extracellular Matrix Adhesion and Cell Cycle Progression

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

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.

 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, [Email Address Removed]

To apply for this position please visit here.

 Please clearly state the name of the DoS and the studentship title that you are applying for on your personal statement.

Please see here for a list of supporting documents to upload with your application.

For more information on the admissions process contact [Email Address Removed].

The closing date for applications is 12 noon on 8^th July 2022. Shortlisted candidates will be invited for interview on 25^th 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.