About the Project
Applications are invited from high-calibre international candidates for a self-funded PhD project in medicinal chemistry and cancer drug discovery with Dr Ali Raoof. This project will focus on the design, synthesis and biological evaluation of novel small-molecule therapeutics for oncology, with the aim of developing chemical tools and lead compounds that can modulate oncogenic pathways, overcome therapeutic resistance, or exploit vulnerabilities in aggressive malignancies.
Based in the Faculty of Biology, Medicine and Health at The University of Manchester, the student will join a collaborative research environment spanning medicinal chemistry, synthetic organic chemistry and cancer biology. The project will benefit from colleagues across Cancer Sciences, the Cancer Research UK Manchester Institute and The Christie Hospital working on pancreatic cancer (Professor Claus Jorgensen), leukaemia (Professor Tim Somervaille) and brain tumours (Professor Petra Hamerlik), all interrogating challenging and yet compelling targets in difficult to treat cancers.
The successful candidate will receive training in medicinal chemistry as the core discipline underpinning drug design, alongside practical experience in multi-step synthesis, compound purification by HPLC and flash chromatography, and structural characterisation by NMR and mass spectrometry. The project will also introduce structure–activity relationship-guided hit-to-lead development, lead optimisation and computer-aided drug design. Synthesised compounds will be assessed using appropriate enzymatic, biophysical and cellular pharmacology assays, with promising molecules progressed to DMPK studies and, where justified, evaluation in relevant in vivo oncology models through established collaborative networks. This project is particularly suited to applicants with a strong background in chemistry, pharmaceutical sciences in particular medicinal chemistry, and an interest in applying chemical innovation to clinically important problems in cancer research.
Eligibility
Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in Chemistry, Medicinal Chemistry, Pharmaceutical Sciences or a closely related discipline. Strong practical laboratory experience in organic synthesis is desirable.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form select PhD Pharmacy and Pharmaceutical Sciences. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester
If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester
Funding Notes
Applications are invited from self-funded students. This project has a Band 2 (medium) fee. Details of our different fee bands can be found on our website View Website
References
- Nicosia, L., Spencer, G. J., Brooks, N., Copland, M., Searle, E., & Somervaille, T. C. P. (2023). Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies. Cancer Cell, 41(12), 2101-2117.e13. doi.org
- Pappalardi, M.B., Keenan, K., Cockerill, M., Kellner, W.A., Stowell, A., Sherk, C., Wong, K., Pathuri, S., Briand, J., Steidel, M., Chapman, P., Groy, A., Wiseman, A.K., McHugh, C.F., Campobasso, N., Graves, A.P., Fairweather, E., Werner, T., Raoof, A., Butlin, R.J., Rueda, L., Horton, J.R., Fosbenner, D.T., Zhang, C., Handler, J.L., Muliaditan, M., Mebrahtu, M., Jaworski, J., McNulty, D.E., Burt, C., Eberl, H.C., Taylor, A.N., Ho, T., Merrihew, S., Foley, S.W., Rutkowska, A., Li, M., Romeril, S.P., Goldberg, K., Zhang, X., Kershaw, C.S., Bantscheff, M., Jurewicz, A.J., Minthorn, E., Grandi, P., Patel, M., Benowitz, A.B., Mohammad, H.P., Gilmartin, A.G., Prinjha, R.K., Ogilvie, D., Carpenter, C., Heerding, D., Baylin, S.B., Jones, P.A., Cheng, X., King, B.W., Luengo, J.I., Jordan, A.M., Waddell, I., Kruger, R.G., McCabe, M.T. (2021). Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nature Cancer, 2, 1002–1017.
- Biarylamide derivatives and their use as PKMYT1 inhibitors. Raoof, Ali; Spyridon-Gavriil, Efthymios; Niculescu-Duvaz, Dan; Brown, Michael; Smithen, Deborah; Fitzpatrick, Christopher; Grytsai, Oleksandr; Aljarah, Mohammed; Lisauskaite, Monika; Burgin, Ryan; Kershaw, Christopher Stephen; Leung, Leo; Hagan, Iain; Marais, Richard; Springer, Caroline. WO2024184550A1.
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