The ability of cells and tissues to modulate rates of gene expression is critical for their ability to respond appropriately to cues during development, maintain normal function during ageing, and combat environmental insults and biological agents such as pathogens. Gene expression is dynamically regulated by molecular switches including reversible protein phosphorylation, which can control mRNA synthesis, processing, and export rates. Interrogating these molecular switches provides insights into the mechanisms of cell decision-making and may yield strategies that could be used to steer cells or tissues away from harmful choices toward more beneficial ones.
Reversible phosphorylation is controlled by the antagonistic activities of protein kinases and phosphatases, often acting in combination with other enzymes, to bring about a change in the genetic programme that determines cell fate. However, understanding when and where these enzymes act during mRNA synthesis remains a significant challenge, particularly in vivo. Interrogating such processes necessitates the use of quick and adaptable methods of interfering with gene function. However, many of the most widely used interventional approaches, such as RNAi or CRISPR-Cas9, operate at the gene or transcript level, which means that the effects of gene perturbation are exhibited over longer time frames than the process under investigation.
In this project, we plan to address these problems using rapid and inducible protein disruption (reviewed Campbell and Bennett, Biochem J. 2016, 473(17):2573-89). This will be achieved by combining genome engineering, optogenetics, and live cell imaging approaches in a developmental model. The student will be embedded within active research groups conducting research highly relevant to the student’s project and will benefit from access to exceptional core facilities and training in next-generation molecular, cell and developmental biology tools in the supervisors’ laboratories, ensuring good career development opportunities for the student.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous experience are particularly encouraged to apply.
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Incomplete applications will not be considered and withdrawn.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”