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MRC DTP iCASE PhD Project: Characterisation of novel niraparib resistance mechanisms in ovarian cancer


About This PhD Project

Project Description

We invite applications from outstanding biological or biomedical sciences graduates for a fully-funded 3.5-year MRC Doctoral Training Programme iCASE PhD studentship, in collaboration with GlaxoSmithKline (GSK), starting in September 2020, based in the Jacqui Wood Cancer Centre in the University of Dundee School of Medicine, Ninewells Hospital & Medical School.

Our translational research team aims to understand the molecular basis of drug resistance in ovarian cancer, where response to chemotherapy treatment is frequently compromised by the development of treatment-limiting resistance (1). Our iCASE studentship will focus on identification of novel mechanisms of resistance to PARP inhibitors (PARPi), building on our published data (2), and more recent identification of differentially expressed candidate genes in unique resistance models.

The student will create novel cell lines to model resistance in patients both with and without BRCA1/2 gene mutations. In collaboration with GSK investigators, novel resistance targets will be prioritised (novelty, actionability and synergy with the GSK drug development pipeline) for detailed experimental validation, comparing chemotherapy response in sensitive and resistant cells, and investigating cross-resistance to additional PARPi, and to structurally and functionally diverse chemotherapy drugs. Targets will be validated using a combination of siRNA transient knockdown and small molecule inhibitor studies. Based on bioinformatics predictions, quantitative phenotypic assays will be used to confirm predicted drug resistance phenotypes, before validated candidate genes are prioritised for prognostic biomarker development. In the final year of the studentship, the student will spend 3-6 months working alongside the GSK oncology R&D team.

Candidates should have (or expect to achieve) a 2.1 Honours degree in a relevant biological or biomedical sciences subject. UK and EU students will receive a full-fee studentship, supplemented by £2500 per annum. Our ideal candidate will be experienced in cell and molecular biology, and familiar with mammalian cell culture techniques. Excellent oral and written communication skills are essential, as is statistical literacy and a genuine passion for translational research.

Informal inquiries and applications (in the form of a cover letter and CV, including contact details for at least 2 academic referees) should be sent to Dr Gillian Smith () and Dr Michelle Ferguson ().

Please note that the deadline for applications is the 13th of March 2020.

References

References:

Vaughan S, Coward JI, Bast RC, Jr., Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719-25.

Vaidyanathan A, Sawers L, Gannon AL, Chakravarty P, Scott AL, Bray SE, et al. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. Br J Cancer. 2016;115(4):431-41.

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