Roles of negative transcriptional regulators in breast cancers

Division of Molecular and Cellular Function, The University of Manchester

Dr Pawel Grzechnik
Dr Sankari Nagarajan

Applications accepted all year round
Self-Funded PhD Students Only

About the Project

Breast cancer is a widespread and life-threatening condition that affects millions of women globally. Understanding the complexity of gene expression associated with this disease is essential for developing targeted interventions that can revolutionize its diagnosis, treatment, and prevention.

Deregulation of transcription factors is one the most common factors contributing to carcinogenesis as precise control of transcription and RNA processing is essential for the correct gene expression. While the activation of transcription is widely studied, knowledge about transcriptional repression is comparatively limited. The downregulation of transcription allows the reduction of gene expression by limiting RNA synthesis. This can be achieved by premature transcription termination, decreased transcription rates or increased promoter-proximal RNA Polymerase II (Pol II) pausing. The persistent presence of Pol II on the gene allows for a rapid shift from an “off” to “on” state when needed. Such transitions are essential for survival strategies including stress responses and cellular signalling.

A successful candidate will study the functions of protein interacting with RPRD (Regulation of Nuclear mRNA Domain-Containing) proteins (RPRD1B, RPRD1A and RPRD2) which have been identified in our lab as negative transcription factors. RPRDs belong to the family of important transcriptional regulators interacting with RNA Polymerase II, are present on actively transcribed genes and their levels correlate with the cellular transcription rates. Most importantly these proteins are heavily overexpressed in breast cancer cells originating from primary and metastasis patients.

Thus, the project will dissect the mechanistic details of how proteins interacting with RPRDs enforce transcription downregulation with a special focus on processes mediating the transition from transcription initiation to elongation in cancer cells.

Our group is based at the University of Manchester, which has a reputation for pioneering research and innovation with 25 Nobel Prize winners. The University was ranked 32nd in the world in the 2024 QS University Rankings and 2nd in the world for social and environmental impact in the THE Impact Rankings. Manchester is a friendly city with award winning museums and world famous football clubs, and has regularly been voted the UK’s best city to live.

Eligibility

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

Before you Apply

Applicants mustmake 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 Molecular Biology 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