Do chromatin remodellers control awakening of hibernating cancer cells?
Closing date: 15/11/2024
Non-Clinical Studentship Project: Do chromatin remodellers control awakening of hibernating cancer cells?
Lead Supervisors: Dr Sankari Nagarajan
Co-Supervisors: Prof. Robert Clarke, Dr Frances Turrell, Dr Anne Armstrong, Dr Hannah Harrison
Applications Deadline: Friday 15th November 2024
Interviews: Friday 17th January 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
Cancer cells adapt to live in the presence of treatment or any selective pressure. This sometimes leads to cancer cells hibernating and lingering in the host tissues by stopping cell division. When environment changes to favourite conditions for cancer cells, they awake and start proliferating. The sleep phase is called dormancy, and the wakeup phase is called awakening. Understanding how cancer cells go through dormancy and awakening is critical in terms of treatments, as the awakened cells are more aggressive, leading to cancer spread to other organs. With the powerful data analyses on proteomics on histone marks, it was previously identified that specific histone modifications change during dormancy or awakening. Some of these marks are specifically controlled by chromatin remodellers which open or close the DNA-histone interactions. Interestingly, chromatin remodelling proteins are specifically altered or lost up to 12-13% in drug relapsed or metastatic breast cancer patients.
Hence, we hypothesise that chromatin remodelling proteins are involved in the control of dormancy and their loss can promote awakening of cells. The activated pathways can be strategically targeted by inhibiting the histone modifiers in patients who have perturbations on chromatin remodelling proteins, supporting stratified targeted medicine.
Using the multidisciplinary approaches of functional epigenomics and immunohistochemistrybased protein analyses on in vivo models with strong expertise of our supervisory team and worldclass collaborators from Institute of Cancer Research (Prof. Luca Magnani and Prof. Cathrin Brisken), the project will allow the student to test if
- chromatin remodellers are involved during dormancy or awakening of breast cancer cells
- inhibitors controlling histone marks can be used as therapeutic strategies to stop awakening of cancer cells, hence control aggressiveness.
This study will lead to better understanding of the role of epigenetic proteins in dormancy/awakening, identify specific markers and novel therapeutic strategies to stop these processes in breast cancer.
Applications for this project are now open. Please complete your application on The University of Manchester 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.
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.
Our Non-Clinical PhD Studentships are usually funded for four years, with funding covering:
- Project running costs
- University tuition fees university tuition fees (at the UK rate, with some scholarships available for high-performing EU/International candidates)
- An annual stipend of £21,000 to help with living costs
Studentships are highly competitive and so we encourage you to contact any supervisors who you are interested in working with before applying for our Non- Clinical PhD Studentships.
International Candidates
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 to high-performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges.
We assess each EU and international candidate’s suitability for a bursary at the application and interview stages.
You must hold, or be about to achieve, a First or Upper Second-class honours degree in a relevant subject. A related Master’s degree is also an advantage.
International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University’s Country Specific information page.
Key dates
- Applications open: 11th October 2024
- Application deadline: 15th November 2024
- Interviews: 17th January 2025
- Start date: September 2025
Useful Links
Submit your application
Interested in applying for this opportunity? Go to The University of Manchester website to submit your application.
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