Closing date: 25/03/2024
MB-PhD Project: Gene regulatory networks driving metastatic progression in oesophageal adenocarcinoma
Applications Deadline: Monday 25 March 2024
Project Keywords: Oesophageal adenocarcinoma; Epigenetic regulation; Metastasis
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB
The project supervisor is offering a PhD in the below area during 2024/2025. Work during the Summer Placement might involve some of this work but could vary.
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.
Find answers to some common questions about our MB-PhD summer placement.
To apply for our MB-PhD summer placement, you must be:
A University of Manchester MBChB student:
- currently studying in Year 1 or 2
A University of St Andrews Medicine BSc (Hons) student on the Manchester course pathway:
- currently studying in Year 1 or 2
International applicants (including EU nationals) must ensure they meet the relevant academic eligibility criteria (including English Language).
Placement weeks will be arranged between students and supervisors over the summer before the start of the next academic year (2-6 September).
University of St Andrews students can apply for funding from their university to cover expenses.
These placements are unpaid but students at The University of Manchester interested in undertaking a summer placement and unable to do so due to financial reasons should get in touch with Georgina Binnie-Wright, Postgraduate Programme Manager, at MCRCTraining@manchester.ac.uk, to discuss.
Students who are interested in this opportunity should send the following details to Georgina Binnie-Wright, Postgraduate Programme Manager, at MCRCTraining@manchester.ac.uk:
- Your name
- Current year of MBChB study
- Are you intending to apply to the MB-PhD programme in future? (Yes/No)
- Are you applying for this opportunity due to a general interest in academic research? (Yes/No)
- 200 words maximum on why you are interested in a placement
- Lab preference(s)
Depending on how much interest is shown, preference may be given to students who are eligible to apply to the MB-PhD programme in the 2024-25 recruitment round.
Expressions of interest should be returned by Monday 25 March 2024.
- Application deadline: 25 March 2024
Find out more about our MB-PhD Studentships which allow you to study a fully-funded PhD alongside your medical degree.
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