Biomarkers for DNA replication stress targeting therapy in glioblastoma and high grade serous ovarian carcinoma

MRC DTP in Precision Medicine iCASE studentships

Up to 2 fully funded studentship positions are available in the College of Medical Veterinary, Medical and Life Sciences.

The iCASE scheme:
• Provide students with experience of collaborative research with a non‐academic partner
• Offer students an experience of at least two distinct research cultures
• Provide access to a wider than usual range of technology, facilities and expertise
• Enable the student to spend a period of time with the non-academic partner (no less than 3 months over the lifetime of the PhD).

The iCASE scheme is intergrated with our MRC-funded Doctoral Training Programme (DTP) in Precision Medicine which involves the student spending at least 3 months over the lifetime of the PhD with a non-academic partner. This is a collobaroative programme with the University of Edinburgh. This DTP addresses key MRC skills priorities in Quantitative Skills (mathematics, statistics, computation, developing digital excellence) as applied to variety of data sources (from ‘omics’ to health records) or Interdisciplinary Skills including imaging, and stratified medicine. The programme has a tiered access model allowing students to undertake a 3.5 year PhD, for students who already have a Masters degree (in a relevant field), or a 4 year PhD for those entering with a BSc Honours (in a relevant field). The mandatory taught training element is a vital aspect of the programme and is designed to ensure students gain skills aligned with the MRC skills priorities outlined above. Students on the 3.5 year programme are required to take 30 credits and those on the 4 year programme 120 credits across the first 3 years, with 40 credits completed in Year 1. Mandatory taught elements will include Statistics, Research Ethics, Innovation and Entrepreneurship, Health Economics, Data Management and Bioinformatics.

Supervisors:
Dr Ross Carruthers, Institute of Cancer Sciences
Dr Patricia Roxburgh, Institute of Cancer Sciences
Dr Ros Glasspool, Institute of Cancer Sciences
Prof Anthony Chalmers, Institute of Cancer Sciences

Industrial Partner: AstraZeneca
Mark J O’Connor
Simon Hollingsworth

Project Summary:
DNA replication stress (RS) is a fundamental characteristic of all cancer cells and is an appealing clinical target due to the aberrant DNA damage response (DDR) pathways active in many tumour cells and the lack of RS seen in non malignant cells. Our laboratory has demonstrated that tumour cells exhibiting elevated RS are more susceptible to the cytotoxicity of DDR inhibitors, whilst clinical trials of these agents are currently underway in glioblastoma (GBM) and high grade serous ovarian cancer (HGSC). Nevertheless robust biomarkers allowing patient selection through identification of tumours exhibiting elevated RS and aberrant RS responses will be necessary for the clinical success of this approach.

This PhD project will develop biomarkers of RS and sensitivity to DDR inhibition using in vitro cell lines, in vivo models and existing patient tumour samples with clinical data, in collaboration with AstraZeneca as an industry partner. It will offer a student the chance to develop expertise in a range of basic and complex novel laboratory techniques, in vivo tumour models, and experience of analyzing genomic and RNA sequencing data. There will be opportunities to submit abstracts to national and international conferences, and a high degree of support and supervision will be available throughout the project.