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(MCRC Non-Clinical) Deconvoluting the epigenetic transition and intratumour heterogeneity in aggressive breast cancers


Faculty of Biology, Medicine and Health

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Dr S Nagarajan , Prof A Sharrocks , Dr R Clarke , Dr Anne Armstrong No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

Breast cancers are the most common cancers in the modern world. Triple negative breast cancers (TNBC) represent one of the cancers of unmet need due to the poor clinical outcome of the patients. The molecular mechanisms behind how this disease becomes aggressive and spreads to other organs of the body (the evolutionary process of metastasis) is poorly characterised. Current knowledge exploring metastasis includes evidences accumulated from cell population-based studies, but ignores the substantial involvement of intratumour heterogeneity. Thus, understanding the molecular alterations which occurs during the establishment of metastasis in a single cell resolution is critical to reveal the key regulators of cancer evolution and development.

Using the cutting-edge and high throughput combination of single cell and functional genomic assays on primary and metastatic tumours from TNBC mouse xenograft models, the project aims to identify the differential changes apart from DNA (called as epigenetic alterations) and transcriptional key drivers which are essential for establishing metastasis. Understanding the epigenetic alterations in pre-metastasised cells on preclinical primary tumour models will reveal the dynamics of most relevant molecular events during metastatic transition in aggressive cancers and decipher the clonal origin of metastasis. This will investigate the influence of intratumour heterogeneity which challenges the efficacy of the existing therapeutic interventions and might help in developing better approaches to treat these poor outcome cancers. This metastasis-specific altered events in the context of tumour heterogeneity can be developed as a potential biomarker for TNBC patients undergoing metastasis to predict poor outcome even from a primary surgical or biopsy tumours. Overall, this study will establish a systematic, unbiased and unique approach of integrating epigenomic and transcriptomic datasets to identify the key drivers and gene signature associated with reprogramming during metastasis in specific clones.

Entry Requirements:
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the CRUK Manchester Centre PhD Training Scheme (MCRC) website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

General enquiries can be directed to [Email Address Removed].

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/


Interview date – 8 January 2021

Funding Notes

Funding will cover UK tuition fees/stipend only (currently at £19,000 per annum) and running expenses. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable a limited number of full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

The duration of this project is four years to commence in October 2021.
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