(MB-PhD) Gene regulatory networks driving metastatic progression in oesophageal adenocarcinoma The University of Manchester in United Kingdom

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. There is a growing realisation that mutational changes 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 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.  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.

Eligibility

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

International applicants (including EU nationals) must ensure they meet the relevant academic eligibility criteria (including English Language). International candidates should contact Dr Georgina Binnie-Wright, MCRC-CRUK Manchester Centre Postgraduate Programme Manager, to discuss fee scholarships available to the highest-performing international applicants at interview.

Before you apply

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.

How to apply

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Cancer Research UK MB-PhD | Biology, Medicine and Health | The University of Manchester