BBSRC Industrial CASE PhD Studentship - Evaluation of the use of imaging agents for drug transporter interaction studies

Faculty of Medical and Human Sciences

University of Manchester

The aim of this project is to explore the potential of magnetic resonance imaging techniques to describe and understand transporter-mediated drug pharmacokinetics in-vivo. The studentship provides full support for tuition fees, associated research costs and a minimum annual tax-free stipend anticipated to be £15, 990. The project will commence October 2010 and is open to UK/EU* nationals only due to the nature of the funding. The project will also feature a placement at AstraZeneca, Alderley Park.

Rationale: Magnetic resonance imaging (MRI) is a non-ionising imaging modality that frequently uses contrast agents to evaluate suspected lesions or monitor response to treatment. Whilst some MR contrast agents are taken up passively by diffusion across the endothelial barrier, others may enter or leave specific cell types through transporter-mediated processes. This latter group of contrast agents offers the possibility to derive characteristics and interactions of the transporters involved.

In recent years, the importance of transporter-mediated interactions on the disposition, safety and efficacy of drugs has become evident but there are difficulties in translating in-vitro interactions to those observed in animals and patients. MRI could potentially bridge this gap by providing a non-invasive imaging probe to investigate the interaction of contrast agents that are known to be taken up by transporters with compounds that may inhibit these transporters.

The specific aims of the project are to:

• Design and implement pre-clinical MRI protocols to measure transporter-mediated pharmacokinetics in-vivo
• Evaluate the transporters involved in the uptake and efflux of MRI contrast agents using in-vitro techniques
• Develop a mathematical pharmacokinetic model to describe the transporter-mediated processes involved in the uptake and efflux of MRI contrast agents
• Assess the utility of MRI techniques to describe and understand transporter-mediated drug-drug interactions pre-clinically and possibly also in patients
• Investigate complementary MRI techniques to assess the functional status of the liver and/or kidneys in the performed studies

This project will be conducted jointly within the Imaging, Genomics & Proteomics Research Group and the Drug Metabolism and Pharmacokinetic Research Group. The successful candidate will be provided with extensive training in imaging, cell biology and pharmacokinetic modelling and will be immersed in a multi-disciplinary research environment.

Upon completion, the candidate would be ideally placed to progress into either an academic or industrial research career. At present there is a shortage of high quality translational researchers with expertise in imaging and pharmacokinetics.

Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in a physical science or alternatively in a biological science with high numerical content. A Masters qualification in a similar area, or previous experience of imaging would be beneficial.

Please direct applications in the following format to Dr Josephine Naish (josephine.naish@manchester.ac.uk) and Dr Jeff Penny (jeff.penny@manchester.ac.uk):

• A CV, including full details of all University course grades to date.
• Contact details for two academic or professional referees.
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Jo Naish or Dr Jeff Penny. Applications are invited up to and including Wednesday 31 March 2010.

*Applicants must be UK/EU nationals who have been permanent UK residents since 1 September 2007 in order to qualify for full funding support.

http://www.medicine.manchester.ac.uk/imaging/

http://www.pharmacy.manchester.ac.uk/

Further PhD project opportunities within the Faculty of Medical and Human Sciences can be found on our 'PhD Opportunities iFrame':

http://www.mhs.manchester.ac.uk/postgraduate/studentships/