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PhD Studentship Imaging Tumour Phenotype and Underlying Genotype Using Hyperpolarized Magnetic Resonance Imaging

Applicants are invited to apply for a PhD position in computational biology at University of Cambridge. Applications are invited up to November 15, 2018.

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.

Professor Kevin Brindle, Head of the Molecular Imaging group, wishes to appoint a student to work on the project entitled: Imaging tumour phenotype and underlying genotype using hyperpolarized magnetic resonance imaging.

We have been developing magnetic resonance imaging (MRI) methods for interrogating tumour cell metabolism using hyperpolarized 13C-labelled cell metabolites. Nuclear spin hyperpolarization can increase sensitivity in the MR experiment by >10,000x. This has allowed us to image the location of labelled cell substrates in vivo and, more importantly, their metabolic conversion into other cell metabolites. These substrates include pyruvate, lactate, glutamine, glutamate, fumarate, bicarbonate, ascorbate and glucose. Reviewed in (1-3). Exchange of hyperpolarized 13C label between lactate and pyruvate has been imaged in various tumour models and this flux has generally been shown to decrease post-treatment and hyperpolarized [1,4-13C]fumarate has been shown to detect subsequent tumour cell necrosis. Tissue pH can be imaged from the ratio of the signal intensities of hyperpolarized H13CO3 and 13CO2 following intravenous injection of hyperpolarized H13CO3 and tumour redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively. Tumour glycolysis can be monitored by measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate and there is evidence that we can also detect pentose phosphate pathway flux from 6-phosphogluconate labelling. In a genetically engineered mouse model of pancreatic cancer we have shown that hyperpolarized [1-13C]pyruvate can be used to follow progression of precursor lesions (4) and more recently in patient-derived orthotopically implanted xenograft models of glioma that flux of 13C label between lactate and pyruvate varies between tumours derived from different patients and that this reflects expression of c-Myc (5). Imaging with hyperpolarized [1-13C]pyruvate has translated to the clinic and this has included studies in Cambridge. The metabolism of these hyperpolarized 13C-labelled substrates, and also novel ones that we are developing, report on various aspects of tumour metabolism, which in turn reflects the mutational status of the tumours. In this project the student will explore the extent to which non-invasive metabolic imaging with hyperpolarized 13C-labelled metabolites can be used to interrogate the underlying mutations that are driving tumour cell proliferation in patient-derived xenograft models of breast, ovarian and brain (glioma) cancer and therefore whether these imaging techniques could be used clinically to inform prognosis and treatment selection.

The student will learn a variety of techniques, including magnetic resonance imaging and spectroscopy; metabolic biochemistry, particularly as it relates to oncology and tumour cell and molecular biology.

Preferred skills/knowledge Applicants should have excellent communication and team working skills with a degree in the physical or biomedical sciences. A Master’s degree is not essential but some laboratory experience would be beneficial.

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.

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.

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.

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

The closing date for applications is 15 November 2018, with interviews expected to take place in December/January.

This project is funded by a Cancer Research UK studentship that includes full funding for University and College fees and a stipend of 19,000 per annum.

No nationality restrictions apply to Cancer Research UK funded studentships. 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.


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