The Cancer Research UK Cambridge Institute (CRUK CI) is a joint venture between the Charity, Cancer Research UK, and the University of Cambridge. The Institute has excellent state-of-the-art facilities and research ranges from basic cancer biology and computational biology through to translational research and clinical application.

Graduate students play a pivotal role in the continuing success of our research programmes and gaining a studentship in the Institute is an excellent opportunity to start a research career in an environment committed to training outstanding cancer research scientists of the future. For further information, go to: https://www.cruk.cam.ac.uk/jobs-and-studentships/postgraduate-study

Dr James Brenton, Head of the research group studying Functional Genomics of Ovarian Cancer, wishes to appoint a student, to commence study in October 2020, to work on the project entitled: Repurposing Existing Drugs as Cancer Therapies

For further information about Dr Brenton’s group, go to https://www.cruk.cam.ac.uk/research-groups/brenton-group

Project details:

The extraordinary genomic complexity of copy-number aberration in high grade serous ovarian carcinoma (HGSOC) has prevented effective molecular stratification in the clinic. We have identified copy-number (CN) signatures that can detect specific patterns of DNA damage response (DDR) from clinical biopsies [1]. These signatures now offer new predictive tests for therapy with PARP inhibitors such as olaparib. PARP inhibitors are currently the only FDA-approved class of DDR inhibiting cancer therapies and are significantly improving survival for women with HGSOC. However, resistance to PARP inhibitor therapy is a significant and growing clinical problem underscoring the need to identify new PARP inhibitor compounds with alternative mechanisms of action. This project will use functional genomic approaches to characterize novel PARP inhibitors identified by Cycle Pharma and the University of Cambridge including using CN signatures to develop biomarkers and mechanisms of action for these medicines. The PhD project will be based in the CRUK Cambridge Institute in the Brenton laboratory and will use experimental approaches based on well characterized HGSOC models including cancer organoids, primary patient samples and unique HGSOC cell lines. The main techniques will include whole genome sequencing analysis, high throughput RNA profiling with L1000 for therapeutic phenotyping [2]and high throughput microscopy for DDR biomarkers. The project has direct translational relevance as identifying new PARP inhibitors has major impact for women with high grade serous ovarian cancer. In addition, the strategy of identifying new activities from existing medicines that have already completed safety testing and entered clinical practice, will ensure rapid transition into therapeutic studies in cancer patients.

Further reading:

[1] Macintyre G, Goranova TE, De Silva D, Ennis D, Piskorz AM, Eldridge M, Sie D, Lewsley LA, Hanif A, Wilson C, Dowson S, Glasspool RM, Lockley M, Brockbank E, Montes A, Walther A, Sundar S, Edmondson R, Hall GD, Clamp A, Gourley C, Hall M, Fotopoulou C, Gabra H, Paul J, Supernat A, Millan D, Hoyle A, Bryson G, Nourse C, Mincarelli L, Sanchez LN, Ylstra B, Jimenez-Linan M, Moore L, Hofmann O, Markowetz F, McNeish IA, Brenton JD. Copy number signatures and mutational processes in ovarian carcinoma. Nat Genet. 2018;50(9):1262-70.https://www.ncbi.nlm.nih.gov/pubmed/30104763

[2] Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, Lahr DL, Hirschman JE, Liu Z, Donahue M, Julian B, Khan M, Wadden D, Smith IC, Lam D, Liberzon A, Toder C, Bagul M, Orzechowski M, Enache OM, Piccioni F, Johnson SA, Lyons NJ, Berger AH, Shamji AF, Brooks AN, Vrcic A, Flynn C, Rosains J, Takeda DY, Hu R, Davison D, Lamb J, Ardlie K, Hogstrom L, Greenside P, Gray NS, Clemons PA, Silver S, Wu X, Zhao WN, Read-Button W, Wu X, Haggarty SJ, Ronco LV, Boehm JS, Schreiber SL, Doench JG, Bittker JA, Root DE, Wong B, Golub TR. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles. Cell. 2017;171(6):1437-52 e17. https://www.ncbi.nlm.nih.gov/pubmed/29195078

Preferred skills/knowledge

The project will require strong computational abilities (or enthusiastic potential) and would be ideal for candidates who have competed both a biology undergraduate degree and a MSc in bioinformatics. Experience in some of the areas mentioned in the project description would be beneficial. The successful candidate must be strongly motivated to drive an independent research project, but also be a highly collaborative individual.

Funding

This project is co-funded by Cancer Research UK and Cycle Pharma. The studentship includes full funding for University and College fees and a stipend of £19,000 per annum.

Eligibility

No nationality restrictions apply to this studentship. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree (or equivalent) in a relevant subject from any recognised university worldwide.

How to apply

All applications need to be made using the University Applicant Portal. Please visit: https://www.graduate.study.cam.ac.uk/courses/directory/cvcrpdmsc for further information about the course and to access the applicant portal.

To complete your on-line application, you need to provide the following:

Reference Request: The names and contact details of two academic referees who have agreed to act on your behalf.

Research: If you wish to be considered for more than one studentship, please enter the names of all of the supervisors you wish to consider your application in the ‘Research summary’ text box. If you only wish your application to be considered by a single supervisor, then please enter their name in the ‘Research Supervisor’ text box. Please describe your past ‘Research experience’ in the appropriate text box.

Course Specific Questions: Your statement of interest (limit of 2,500 characters) should explain why you wish to be considered for the studentship and which qualities and experience you will bring to the role. Please also state how you learned of the studentship.

Supporting Documents: Please upload your CV (PDF file), which should include a list of the examinations taken at undergraduate level and if possible, your examination results

Deadline

The closing date for applications is 30 November 2019, with interviews expected to take place in January 2020.

Please quote reference SW21187 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

SALARY
£-£
REFERENCE
SW21187
CATEGORY
Studentships
PUBLISHED
22 Oct 2019
CLOSING DATE
30 Nov 2019
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