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Dear BB, We have a funded PhD studentship position that we must fill with some urgency (the grant must start by 1st Feb 2010). Please see details below, and this link: http://www.bmb.leeds.ac.uk/staff/tae/YCR_advert.pdf This is a collaboration between the Department of Chemistry and the Faculty of Biological Sciences at the University of Leeds. There is quite alot of flexibility in which direction the student may wish to push the project from synthetic chemistry to experiment structural biology to modelling, and we are therefore open to applications from students with a broad range of backgrounds. I must, unfortunately, stress that funding body requirements state that this position is only open to UK/EU students. I am happy to field informal enquiries at first, but a formal application must then be made. Cheers Ed ______________ T.Edwards Ph.D. Garstang 8.53d Astbury Centre for Structural Molecular Biology University of Leeds, Leeds, LS2 9JT Telephone: 0113 343 3031 http://www.bmb.leeds.ac.uk/staff/tae/ Research is what I'm doing when I don't know what I'm doing. ~Wernher Von Braun Development of Synthetic α -Helix Mimetics as Potent Anticancer Agents Yorkshire Cancer Research funded Project Studentship Dr A. Wilson, Dr T. Edwards and Dr R. Jackson. University of Leeds The purpose of this project is to develop a RULE-BASED APPROACH for the design and synthesis of inhibitors of key protein-protein interactions (PPIs) involved in the development and progression of cancer. The project is concerned with the development of a series of scaffolds designed to act as α-helix mimetics. These scaffolds are amenable to high-throughput solidphase synthesis and thus the generation of libraries. We have recently shown that these scaffolds can be functionalised such that they inhibit the p53-hDM2 interaction (an oncogenic target) with high (μM affinity). The student will develop aromatic oligoamides as proteomimetic inhibitors of three cancer targets: p53/hDM2, Bcl-xL/BAK and Mcl- 1/NOXA-B. Inhibitors of the hDM2/p53 interaction are being sought to decrease tumour growth, with potential clinical applications in a broad range of cancers, including breast cancer (more than half of human cancers express a mutant p53). Bcl-xL and Mcl-1 are members of the Bcl-2 family of proteins and have also been proposed to be a means of intervention against various cancers including prostate cancer and small cell lung carcinoma. The goals of this project are i) to optimise small molecules that mimic these α-helical sequences and bind with high affinity and selectivity to their target protein, inhibiting the native PPI; ii) use structural and molecular biology and biophysics to understand what discriminates a high affinity ligand from one with low affinity. This will provide a starting point for drug development. This multidisciplinary project will provide opportunities for the student to receive training in organic synthesis in addition to molecular biology, crystallography and NMR, molecular modelling and biophysical analyses. The stipend would be at the standard EPSRC rate (~ £13290 pa for 2009/10). Applications for this 3 year studentship should be directed to Tanya Wainwright, School of Chemistry, University of Leeds, Leeds, LS2 9JT and can be made online via the following link: http://www.chem.leeds.ac.uk/newRPG/RPGhowToApply.htm (Please note: only EU applicants can be considered for this award) Please contact Dr. T. Edwards ([log in to unmask]) or Dr. A. Wilson ([log in to unmask]) for further details about this project.