Closing date: 07/03/2025
MB-PhD Project: Gene regulatory networks driving metastatic progression in oesophageal adenocarcinoma
Lead Supervisors: Prof. Andrew Sharrocks
Co-Supervisors: Prof. Yeng Ang, Dr Jamie Weaver
Applications Deadline: Friday 7th March 2025
Project Keywords: Oesophageal adenocarcinoma; Epigenetic regulation; Metastasis
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB
PhD Project Outline
Oesophageal adenocarcinoma (OAC) incidence is increasing and yet survival rates remain very poor. There are limited treatment options, especially for metastatic disease, which is especially problematic as patients usually present with late stage disease. Thus understanding the molecular basis to metastatic disease is a clear unmet need.
There is a growing realisation that mutational changes in the genome are unlikely to explain how cells transition to the metastatic state and instead, epigenetic and associated gene regulatory changes likely play a major role in this transition. This project therefore aims to test this hypothesis and will identify and characterise the gene regulatory networks that define and sculpt the metastatic state in OAC cells through impacting on the regulatory chromatin landscape.
This project will start with patient material and will use matched patient tumour samples to study disease progression. We have an ongoing rapid autopsy study established for sample collection. A range of ‘omic approaches will be implemented to define the regulatory pathways relevant to tumour metastasis. Regulatory networks will be derived through bioinformatic interrogation and subsequent work will validate a key regulator in cell line models by loss and gain of function approaches coupled to molecular, cellular and ‘omic methodologies. Importantly we will revalidate the mechanisms we uncover by integrating further patient derived data.
By focussing on the underlying chromatin landscape, we will uncover the regulatory events that lead to acquisition and maintenance of the OAC metastatic state. This project will have direct clinical implications as we will identify potential targets and pathways for therapeutic intervention in OAC patients with metastatic disease. We will also establish molecular signatures and biomarkers for targeting treatment in a personalised manner.
About Prof. Andrew Sharrocks (project Lead Supervisor)
Professor Andy Sharrocks was appointed to the role of Associate Dean for Research Technology in October 2019, responsible for research technology development and infrastructure in the Faculty.
He is based in the Division of Molecular and Cellular Function, where his research interests include signal-mediated gene regulation and eukaryotic transcriptional control in relation to oesophageal cancer and stem cell differentiation.
Professor Sharrocks achieved an undergraduate degree in Biochemistry from Sheffield University and continued his studies there to complete a PhD studying prokaryotic transcriptional control mechanisms.
He subsequently continued his work on prokaryotic transcription factors in his first postdoctoral position, and moved to the Max Planck Institute in Freiburg, Germany to study eukaryotic transcriptional control mechanisms.
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.
My goal is to make fundamental discoveries about the molecular makeup of oesophageal adenocarcinoma with a view to identifying future therapeutic possibilities. In this context, training of the next generation of clinical researchers is an important goal.
The lab has a mix of experienced Postdocs (3), Phd students (3) and technical support. We regularly have additional rotation students. We operate an inclusive environment and traditionally have had a multinational composition with people from diverse backgrounds.
I expect lab members to be genuinely interested in their research topic and dedicated to executing their experimental programme. The most important attribute is dedication and commitment. I hold regular biweekly meetings with students and operate an open door policy for more regular discussions. Students are expected to attend lab meetings and journal clubs and relevant seminar programmes, and also to regularly present their own work and network with others.
Each student is treated as an individual and the degree of independence and help is tailored to the particular person. The overall ethos is to quickly get the student up to speed and capable of driving their own project and following up on their own ideas.
I mentor my students both during and after they have left the laboratory. I regularly advise past members of the lab. My co-supervisor, Prof Ang, provides continual mentoring to clinically qualified students graduating from my lab.
Hard work is encouraged but not at the expense of a reasonable work-life balance. The key to that is planning and focus while at work, and this will be encouraged.
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 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
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.
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