Closing date: 07/03/2025
MB-PhD Project: Multiomic investigation of the molecular mechanisms during differential treatment response in breast cancers
Lead Supervisors: Dr Sankari Nagarajan
Co-Supervisors: Dr Sumitra Mohan, Prof. Robert Clarke, Prof. David Wedge, Prof. Cliona Kirwan, Dr Ciara O’ Brien
Applications Deadline: Friday 7th March 2025
Project Keywords: Cancer reprogramming; Lobular breast cancers; Proteomics; Genomics; Epigenomics
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB
Project Outline
Lobular breast cancers represent one of the understudied cancers but of unmet need, due to their poor response to targeted therapies. Failure in drug response is often associated with differential molecular changes in cancer cells according to the origin of the tumour (ductal or lobular), either associated with DNA sequences (genetic) or other than DNA that affect gene expression (so-called epigenetic alterations). Understanding the coupled genetic and epigenetic reprogramming is critical to reveal the key regulators of treatment response. However, this interactive reprogramming is poorly understood in any cancers, let alone lobular cancers. Moreover, our current knowledge on these cancers includes evidence accumulated from in vitro-based studies which doesn’t properly replicate the patient samples.
This project aims to understand the previously unknown lobular-specific genetic and epigenetic reprogramming via studying gene alterations, proteomic interaction landscape and changes in the activity and expression of coding and non-coding RNAs (enhancer RNAs, eRNAs) from gene regulatory DNA elements called enhancers on primary tumour tissues. Our study will explore the following:
- Identify the gene alteration profiles of the tumour samples
- investigate the mutation-specific protein interactome and expression of eRNAs
- validate and assess the function of differential protein network and eRNAs
Importantly, our comparative analysis with lobular and ductal samples for specific gene mutations will allow us to identify mechanisms of differential treatment response to already existing therapies, which can indicate potential effective therapeutic approaches.
The proposed study will utilise a multidisciplinary supervisory team with lot of training opportunities for students in targeted genetic profiling, interaction proteomic analyses and high throughput transcriptional profiling. We successfully obtained access to lobular and ductal tumour samples with matched FFPE and frozen material from Breast Cancer Now Tissue biobank for this study. This will be an unbiased one-of-a-kind study investigating the interactive genetic and epigenetic reprogramming in controlling treatment response.
About Prof. Sankari Nagarajan (project Lead Supervisor)
Nagarajan’s lab is interested in unravelling the mechanisms of enhancer regulation and the role of transcription factors in mediating the progression to drug resistance and metastasis in aggressive cancers. Dr Sankari Nagarajan’s lab utilise single cell analyses, functional genomic technologies, quantitative chromatin-based proteomics and CRISPR-Cas9 assays to decipher the mechanisms of transcription. The lab work on the following projects:
1. Understanding the role of chromatin-associated proteins in driving endocrine resistance in breast and prostate cancers
2. Deciphering the activity of enhancers and transcription factors regulated by chromatin remodelling complexes
3. Single cell epigenomics to investigate the molecular mechanisms of metastasis in aggressive cancers
4. Enhancer-derived RNAs as markers for enhancer regulation in aggressive breast cancers
About the lab group
Find out more about the lab group involved in this project and how we support your wellbeing, learning and career development.
I would like to explore how cancer cells can become aggressive and develop themselves so cleverly to escape from therapies. Genomics and epigenetics of cancers are always studied separately, but would they drive cancer together?
The research lab you will end up with is very important in shaping your career and goals of your life. Nagarajan lab is just established with young people who are quite vibrant, enthusiastic and treat each other friendly. Our lab is communicative and very supportive. It is one of the labs where people meet often outside for coffee, drinks and dinner.
I expect the student to be more interactive in the meetings. There is no question called as stupid question up to me. I also expect the student to develop the project with their own ideas. Looking forward for a productive collaboration between the student and the supervisor.
I really love the independence I have experienced since my Postdoc. I would like to guide my student to explore the same. I will support their career path as much as possible and they will be provided with independence to choose what this should be.
I run mentorship schemes for my Division. In addition to being a mentor myself to the student, I will make sure the student gets another mentor that will provide guidance on anything they need help with.
I recommend no work out of hours and during weekends. I highly recommend everyone in my lab to have their own life and spend more time with family. Work smart but not too hard.
Key information
Find answers to some common questions about our MB-PhD Studentships.
To apply to intercalate onto the PhD in Cancer Sciences component of the MB-PhD, you must meet the below criteria and satisfy the general requirements for permission to intercalate set by your institution, including passing all components of the MBChB at first attempt in the year prior to intercalation.
A University of Manchester MBChB student
- holding a BSc (hons) 2.1 or above in a relevant subject and in year 2 or year 3 of the MBChB or year 1 or year 2 of GEM; or
- currently studying in year 3 of the MBChB or year 2 of GEM
A University of St Andrews Medicine BSc (Hons) student on the Manchester course pathway:
- holding or predicted a BSc (hons) 2.1 or above and be intending to intercalate straight onto the MB-PhD ahead of your arrival in Manchester or by no later than between year 3 and year 4 of the Manchester MBChB programme
A University of Leeds MBChB student:
- currently studying in year 3 of the MB ChB
International applicants (including EU nationals) must ensure they meet the relevant academic eligibility criteria (including English Language).
The PhD component of the MB-PhD studentship is usually funded for three years, or four years in exceptional circumstances with prior agreement of MB-PhD Committee and supervisory team.
The studentship covers:
- An annual stipend of £21,000 per year to help with living costs
- Full funding for your PhD tuition fees (at the UK rate, with fee bursaries available for high-performing EU/International candidates)
- PhD project consumables and running costs, including costs for researcher development such as conferences and travel
- MBChB tuition fees (at the UK rate) for a maximum of four years
Here are our quick steps to apply for our MB-PhD:
1. Eligibility
First, you need to check you are eligible to apply for an MB-PhD. Please see the eligibility tab (above) to read all criteria.
2. Contact supervisors
You can explore the range of MB-PhD opportunities that are open to application on our Research Opportunities webpage.
We encourage you to contact the supervisor of any MB-PhD projects that you are interested in before starting your application. Having these conversations will help you to get a feel for the different research themes and projects on offer.
3. Register
Register to apply for our MB-PhD opportunities using the Postgraduate Application Form. You must create an account to register.
4. Create a new application
When you create a new application make sure you select the following:
- Academic Career – Postgraduate Research
- Mode of Attendance – Full-time
- Program Description – search for MB-PhD and then select the MB-PhD Programme
- Candidates apply for the MB-PhD programme – under ‘Research Title’ list MB-PhD Programme. You can provide supervisor preferences/research interests in your accompanying supporting statement and these will be considered at and after interview
- If you are shortlisted, you’ll be interviewed by the MB-PhD Programme Directors and Education Committee before being accepted onto the programme “in principle”. You will be matched with a supervisor based on your interview performance and project/research preferences
- If successful at interview, you will be asked to meet with a nominated MB-PhD supervisor in the subsequent week for them to review and approve your PhD offer
- For funding sources, please include the following information:
– Select ‘Yes’ from the drop-down
– Type of Funding: University of Manchester Scholarship
– Awarding Body: Cancer Research UK MB-PhD
– Status of Funding – Awarded
– Funding Covers – Fully Funded
– Leave the remaining boxes blank
5. Supporting documents
Your application form must be accompanied by several supporting documents:
CV
This should include:
- qualifications (GCSE, A-level or equivalent, and any higher education qualifications, including grades, and your current programme)
- academic prizes, research projects, and academics interests
- extracurricular interests, and activities and positions of responsibility relevant to your application
The information you provide in your CV will be considered in relation to widening participation, and/or university access policies, to ensure that all applicants are treated fairly.
Supporting statements
This should be 1,000 words maximum and include your reason for applying to the MB-PhD programme and your interest and suitability for the project. You can include project/research interest/s here and these will be considered at and post-interview.
References
You need to list two referees, one of which must be an academic referee from The University of Manchester, The University of Leeds or the University of St Andrews-Manchester pathway MBChB programme.
This could be a:
- Clinical debrief tutor
- PEP tutor
- Literature research project supervisor
- PPD tutor
References cannot be submitted by a supervisor named on the project you are applying for.
Supporting documents can be uploaded and submitted with the online application form.
If you have any issues, your supporting documents can be sent directly to the Doctoral Academy Admissions Team at admissions.doctoralacademy@manchester.ac.uk, CC’ing in mcrctraining@manchester.ac.uk.
6. Acknowledgement and review process
Once you have submitted your application form, we will email you with an acknowledgement.
We will review your application after the application deadline and once we’ve received all your supporting documents. If successful at interview, we will also share your application with a nominated supervisor(s) to review.
7. Interviews
We will email you if you are invited to interview.
Interviews will take place at the Oglesby Cancer Research Building in Withington in Spring 2025.
8. Applying to intercalate
UoM MBChB students must complete an intercalation Expression of Interest form by Friday 24th January 2025 (we may be able to consider late applications to intercalate in exceptional circumstances). This form is available on 1MedForms via the following link: https://www.onemedforms.manchester.ac.uk/
UoL MBChB must apply to intercalate via UoL processes by Friday 24th January 2025.
University of St Andrews Manchester pathway students can contact mcrctraining@manchester.ac.uk for guidance.
Key dates
- Intercalation deadline: Friday 24th January 2025
- Application deadline: Friday 7th March 2025
- Interviews: w/c 28th April 2025
- Start date: September 2025
Useful Links
MB-PhD Studentships
Find out more about our MB-PhD Studentships which allow you to study a fully-funded PhD alongside your medical degree.
Get in Touch
Contact Dr Georgina Binnie-Wright, Postgraduate Programme Manager.
A Day in the Life of an MCRC MB-PhD Student
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