Deciphering the expression of regulatory noncoding RNAs specific to metastasis in breast cancers

Closing date: 04/04/2025

CRUK Black Leaders in Cancer Non-Clinical PhD Scholarship: Deciphering the expression of regulatory noncoding RNAs specific to metastasis in breast cancers

Lead Supervisors: Dr Sankari Nagarajan
Co-Supervisors:
Prof. Robert Clarke, Prof. Andrew Sharrocks, Prof. David Wedge, Prof. Cliona Kirwan

Applications Deadline: Friday 4th April 2025
Interviews: Week commencing 28th April 2025
Non-Clinical Studentship start date: September 2025

Project Keywords: Dormancy, Breast cancer epigenetics, Chromatin remodelling
Research Opportunity: Non-Clinical Studentship leading to the award of PhD

Project Outline

Triple-negative breast cancers (TNBC) represent one of the cancers of unmet need due to their aggressive nature, as the disease spreads to other organs of the body (the process of metastasis). Metastasis is associated with important molecular changes in cancer and stromal cells, either associated with DNA sequences (genetic) or other than DNA that affect gene expression (so-called epigenetic alterations). However, current knowledge about metastasis includes evidence accumulated from in vitro-based studies on unpaired primary or metastatic tumour samples and often ignores the substantial involvement of patient-specific alterations. Thus, understanding the molecular alterations which occur during the establishment of metastasis is critical to reveal the key regulators of cancer evolution.
This project aims to understand the previously unknown metastasis-specific epigenetic reprogramming via studying the changes in the activity and expression of non-coding RNAs (enhancerRNAs, eRNAs) from gene regulatory DNA elements called enhancers on matched primary tumour and lymph node metastasised tissues from same patients. Our proposed study will explore the following:
· Identify the gene alteration profiles of the tumour samples
· investigate the metastasis-specific expression of eRNAs
· validate and assess the function and targeting of eRNAs
Importantly, our paired analysis will allow us to model a timeline of epigenetic alterations during tumour evolution, which can indicate potential causalities of these disease processes.
The proposed study will utilise a high throughput transcriptional profiling by looking into the open single stranded DNA using a technique called as Kethoxal-assisted single stranded DNA-sequencing (Kas-seq). We successfully obtained access to 15 TNBC patient samples with matched frozen material from Breast Cancer Now Tissue biobank for this study. This will be an unbiased one-of-a-kind study considering the lack of availability of frozen and paired patient material for investigating epigenetic reprogramming, emphasizing integrative pathology (one of the MCRC-CRUK Manchester Centre strategy) and personalised medicine.

Applications for this project are now open. Please complete your application on the Windsor Fellowship website.

About Dr Sankari Nagarajan (project Lead Supervisor)

Dr. Nagarajan is an internationally known breast cancer biologist working on estrogen receptor-positive breast cancer epigenetics and bioinformatics on next generation sequencing technologies. Her vision is to understand the transcriptional vulnerabilities of aggressive cancers to improve personalised therapies and to support the development and well-being of students and staffs. She sits as a council member of EACR, Breast Cancer Now biobank and grant committee, Lobular Breast Cancer UK, etc. She is a strong ambassador of cancer patient engagement and women in science. Her lab is supported by CRUK Career Establishment Award and Breast Cancer Now project grant.

Find out more

Headshot of Prof. Sankari Nagarajan

Key information

Before submitting an application, please ensure you have read the information below about the funding arrangements and eligibility for Non-Clinical Studentships.

We also encourage you to get in contact with the lead supervisor to discuss the project and any particulars.

Further information is available on the Non-Clinical PhD Studentships webpage.

Fees and Funding
Eligibility
How to apply
Applications Timelines

Useful Links

Submit your application

Interested in applying for this opportunity? Go to the Windsor Fellowship website to submit your application.

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