PhD Studentship: Fully Funded 3-year PhD Studentship in the North Wales Medical School

North West Cancer Research Institute

The role of protein lactylation in cisplatin-resistant ovarian cancer via targeting of monocarboxylate transporters (MCTs)

Dr Jonathan Blank and Dr Christopher Staples

Applications are invited for a three-year PhD studentship within the North West Cancer Research Institute (NWCRI), part of the North Wales Medical School at Bangor University. The studentship is funded by Health & Care Research Wales, which covers the maintenance stipend (approx. £20,015 per annum for 3 years), North West Cancer Research, which covers bench fees (£6,000 per annum for 3 years), with the School covering the full cost of tuition fees. The studentship will commence 1^st April 2025.

The NWCRI focuses on the molecular basis of drug and radiation sensitivity, with expertise in DNA replication stress and repair mechanisms, oncogenic developmental factors, and cancer metabolism. The successful applicant will join an established PhD programme and interact with cancer pharmacologists and cell biologists at the cutting edge of their field of research in well-equipped laboratories.

Project: The function of protein lactylation in cisplatin-resistant ovarian cancer via targeting of monocarboxylate transporters (MCTs)

Cancer cells preferentially metabolize glucose to lactate to support high proliferation rates. In turn, lactate export is required to prevent cytotoxic effects associated with intracellular lactate accumulation. The monocarboxylate transporters (MCT1-4) mediate lactate transport across the plasma membrane. MCT1 and MCT4 are upregulated in various cancer types and predict poor prognosis and increased mortality. Lactate export by MCTs is essential for the survival of glycolytic tumours, and small molecule inhibition of MCTs is a pre-clinically validated approach to treat cancer. MCT1-selective inhibitors have been evaluated clinically and shown promising activity in cisplatin-resistant ovarian cancer. We will characterise the reliance of cisplatin-resistant ovarian cancer cell models (which we show are sensitive to MCT1 inhibition) on MCT expression, and the effects of MCT inhibitors on DNA damage repair mechanisms. Techniques will include microscopy of components of the MRN complex involved in DNA damage repair, including MRE11 and NBS1, which are lactylated in glycolytic cancer cells. These studies will help define the link between MCTs, lactate induction, and chemotherapeutic resistance.

Person Specification Requirements

• Bachelor’s degree (2i or higher) or a Master’s degree in a relevant discipline (e.g. biomedical sciences, biochemistry, molecular cell biology).
• Strong work ethic and genuine enthusiasm for research, with ability to work both independently and collaboratively.
• Significant experience in laboratory bench work and cell culture is highly desirable

How to Apply

All applications must be received by 15^th March 2025 through our online application system (you will be routed to this by clicking on the above 'Apply' button) and include the following documents:

1. Curriculum Vitae: No longer than two pages. Where appropriate, this should also include proof of English Language Competency (7.0 IELTS minimum).
2. Covering letter: Include motivation for applying for PhD, career aspirations, and any reasons that make you particularly suited to undertaking this project.
3. References: All applications require two academic references in support. Candidates must approach referees themselves and include the references with their application.

Further Information

Informal enquiries about the studentship should be directed to Dr Jonathan Blank (j.blank@bangor.ac.uk) and Dr Christopher Staples (c.staples@bangor.ac.uk). Please include your CV and brief summary of your research interests.

Closing date: 15th March 2025

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