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PIM kinase-targeted therapies: improving sensitivity through identification and modulation of cross-talking pathways
University of Dundee
College of Medicine & Dentistry
Dr D W Meek
Dr N M Kernohan
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
This research project is one of a number of projects at this institution. It is in competition for funding with one or more of these projects. Usually the project which receives the best applicant will be awarded the funding. Applications for this project are welcome from suitably qualified candidates worldwide. Funding may only be available to a limited set of nationalities and you should read the full department and project details for further information.
PhD Research Project
This project is one of ten (10), four-year PhD Studentships funded by Medical Research Scotland (http://www.medicalresearchscotland.org.uk/funding.htm) and delivered jointly by the named University and Company. The Studentship will provide the first-class academic and commercial training needed to equip the successful student for a science career in an increasingly competitive market.
Improving the sensitivity of a novel PIM kinase-targeted therapeutic agent, CXR1002, through identification and modulation of cross-talking pathways - delivered by the University of Dundee and CXR Biosciences Ltd (http://www.cxrbiosciences.com/).
Academic supervisor: Dr David Meek (http://www.dundee.ac.uk/medschool/staff/david-meek/); Company supervisor: Dr Anna Barnett
This project will focus on understanding the cellular factors that influence pharmaceutical regulation of the PIM protein kinase family (PIM-1, -2 and -3). It is based on an ongoing collaboration between Dr David Meek at the University of Dundee and Dr Anna Barnett at CXR Biosciences in Dundee.
The PIM kinases have been implicated in several diseases: they are involved mainly in cancer where they behave as potent oncogenes, but they also contribute to diseases such as myocardial infarction, arteriosclerosis, rheumatoid arthritis, diabetic retinopathy, and age-related macular degeneration retinopathy. Pharmaceutical control of PIM activity is therefore likely to have a significant impact on these conditions. However, our knowledge is limited concerning the full extent of PIM signalling and its cross-talk with other growth and survival pathways. It is important to understand these connections because other signalling pathways could influence the outcome of, or compensate for, inhibition of PIM activity. This, in turn, may affect the efficacy of PIM-targeted therapeutics.
To address these issues we shall use complementary approaches to identify signalling pathways that interact with the PIM pathway: this will include carrying out a synthetic lethal screen in which an siRNA library will be used to detect and identify signalling components which, when eliminated, stimulate cell killing only when PIM activity is inhibited (using small molecule inhibitors or RNAi). In parallel, the effects of targeting specific signalling components in pathways predicted to influence PIM function will be carried out. From a therapeutic perspective, the identification of cross-talking pathways will provide crucial information that will impact on the development and testing of compounds aimed at regulating PIM activity and, consequently, cell survival.
The project will provide experience of working within a collaborative framework in both a vibrant academic environment and a small biotech company. It will also provide technical and intellectual training in key areas of signal transduction and drug development.
Interviews will be held mid- end-March 2012
The PhD Studentship provides: an annual tax-free stipend of £16,000, increasing to £16,500 over the four years; tuition fees at UK/EU rates only; and consumables. Please note international fees are not covered.
Hogan C, C Hutchinson, L Marcar, D Milne, M Saville, J Goodlad, N Kernohan and D Meek. (2008) Elevated expression of oncogenic Pim protein kinases induces the p53 pathway in cultured cells and correlates with high levels of Mdm2 in mantle cell lymphoma. J Biol Chem, 283, 18012-18023.
Nawijn MC, A Alendar & A Berns. (2011) For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer 11, 23-34 (2011)
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