About the Project
Background - Prostate cancer (PC) is the second commonest cause of cancer deaths in British males with nearly 10,000 deaths per annum. There are 36,000 new cases reported every year and this figure is predicted to double over the next 20 years, placing considerable strain on our healthcare sector. This problem is further exacerbated by the ineffectual androgen deprivation therapy (ADT) currently available for the treatment of locally advanced PC, which inevitably progresses to castrate-resistant prostate cancer (CRPC). Chemotherapy with docetaxol or carbazitaxol only prolongs life in CRPC patients by weeks, thus a platform technology that can selectively deliver therapeutic payloads more effectively to target CRPC tumours is urgently needed.
Project Objective - The principal objective of this studentship is to develop a new platform technology for the efficient delivery of a chemotherapeutic payload to prostate cancer cells. This will involve the synthesis of a trimodal delivery system comprising a targeting group, a cell uptake enhancing module linked to a chemotherapeutic. This is a collaborative Chemical Biology project that will involve extensive interaction between Glenn Burley’s synthetic group and Hing Leung’s oncology group based at the Beatson Institute for Cancer Research.
.
Academic Environment - The student undertaking this project will receive unparalleled experience in all aspects of modern chemical biology within our industrially-facing interdisciplinary collaboration. Dr Glenn Burley has extensive experience in small molecule synthesis, solid phase peptide/nucleic acid synthesis and microfluidic device fabrication to culture prostate cancer cells. Cell-based experiments will be conducted n the synthetic biology laboratory of Dr Michele Zagnoni whose group has developed a high-throughput microfluidic platform to analyse cell uptake and cytotoxicity. Tissue and in vivo work will be conducted in the world-leading oncology group of Prof. Hing Leung (Beatson Institute). Prof. Leung has access to state-of-the-art facilities and expertise to assess and quantify the selectivity of cell uptake and the efficiency of the dose and toxicity in castrate-resistant mouse models. In addition, the student will collaborate with Chemical Biology groups based at GlaxoSmithKline’s (GSK) Stevenage site.
References
1. Smith, L.D., Dickinson, R.L, Lucas,C.M., Cousins, A., Malygin, A.A., Weldon, C., Perrett, A.J., Bottrill, A.R., Searle, M.S., Burley, G.A., Eperon, I.C. "A targeted oligonucleotide enhancer of SMN2 exon 7 splicing forms competing quadruplex and protein complexes in functional conditions" Cell Reports, 2014, 9, 193-205 .
2. Fallows, A.J., Singh, I., Dondi, R., Cullis, P.M. Burley, G.A. "Highly efficient synthesis of DNA-binding polyamides using a convergent fragment-based approach" Organic Letters, 2014, 16, 4654-4657.
3. Singh, I., Wendeln, C., Clarke, A.W., Cooper, J.M., Ravoo B.J., Burley, G.A. "Sequence-selective detection of double-stranded DNA sequences using pyrrole-imidazole polyamide microarrays" Journal of the American Chemical Society, 2013, 135, 3449-3457.
4. Rajan, P.; Sudbery, I. M.; Villasevil, M. E. M.; Mui, E.; Fleming, J.; Davis, M.; Ahmad, I.; Edwards, J.; Sansom, O. J.; Sims, D.; Ponting, C. P.; Heger, A.; McMenemin, R. M.; Pedley, I. D.; Leung, H. Y. Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Eur. Urology 2014, 66, 32-39.
5. Ahmad I, Patel R, Singh LB, Nixon C, Seywright M, Barnetson RJ, Brunton V, Muller WJ, Edwards J, Sansom OJ, Leung, H. Y. HER2 overcomes PTEN (loss) induced Senescence to cause Aggressive Prostate Cancer. Proc. Natl. Acad. Sci., 2011, 108, 16392.
Continue with Facebook
