Understanding the causes and consequences of heterogeneous regulation of translation elongation in disease

About the Project

The interface between biochemistry and cell biology is a major scientific challenge; while we can dissect complex biological mechanisms in vitro, studying them in the context of a living cell is more difficult. This issue is even more challenging when we consider cell-to-cell heterogeneity. Methodological advances in studying biology at the single cell level have revealed heterogeneity within various model systems. To advance our knowledge of heterogeneity further, we need innovative technological advances to study molecular changes at the single cell level. We have recently shown that colorectal cancer cells exhibit unexpected molecular heterogeneity in the way they respond to some chemotherapies. This heterogeneity sees a subset of cells slowing their rates of translation elongation via an unknown signalling pathway. Translation elongation has not been previously analysed at the single cell level, in part due to a lack of tools to enable this. However, our observations provide evidence that this heterogeneity exists and could explain different response to chemotherapy. Importantly, we have also developed novel methods to analyse this heterogeneity in multiple model systems, including longitudinal analysis of living cells and within tissues from cancer patients.

This studentship will use models of colorectal cancer as a platform to investigate heterogeneous regulation of translation elongation. This will be directly relevant to colorectal cancer, where elongation rates are commonly upregulated, but also other cancers and disease states with elongation dysregulation. The student will determine how heterogeneity arises, what the consequences of heterogeneity are and explore how pervasive this phenomenon is. Our aim is to understand the drivers of heterogeneity and how their modulation could benefit disease management by altering the fate of specific subpopulations of cell. The project design and supervision provided during this studentship will allow the student to develop technical and transferable skills for their future careers.

Eligibility

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in a subject related to biological sciences.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cancer sciences Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

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: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website View Website