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Design, synthesis and evaluation of next-generation nucleoside analogues


   Faculty of Natural Sciences

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  Dr G J Miller  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

All viruses, irrespective of the disease they cause, have to replicate in order to survive. Drugs that block viral RNA or DNA replication by mimicking the natural building blocks of RNA and DNA (A, C, G, T/U) are known as nucleoside analogues. There are three distinct features of nucleosides that make them the preferred treatment for an infectious disease where a nucleoside is available: high barrier to resistance, broad spectrum of activity and high efficacy. This can be observed in the treatments of HSV (Aciclovir and Ganciclovir), HIV (Tenofovir, Zidovudine, Abacavir Emtricitabine and Lamivudine), HBV (Entecavir, Tenofovi, Adefovir, Lamivudine and Telbivudine) and HCV (Sofosbuvir). Most recently, Remdesivir has been approved for the treatment of SARS-Cov-19,[1] and Molnupiravir as an investigational treatment for the same viral infection.[2]

Your PhD project will involve the design and chemical synthesis of a new classes of nucleoside analogue to enable their evaluation in conjunction with the industrial partner on the project. Here we have a successful collaboration with Riboscience LLC https://www.riboscience.com),[3a,b] a US Biotech, concerned with the discovery of new nucleoside analogues.

You will receive training in organic synthesis, carbohydrate chemistry and in the design and development of complex, multi-step routes to important nucleoside targets. Transferable skills such as reporting of results orally and in writing, time management, project planning and management will also be developed.

Qualifications: Applicants should have or expect at least a good 2(i) honours degree (or an equivalent degree) in Chemistry. Any experience in synthetic organic or carbohydrate chemistry is a plus. 

Studentship available from October 2021.

Contact for further information: For informal inquiries regarding the project please contact the academic lead, Dr Gavin J. Miller: [Email Address Removed] and include a CV. A formal application must be submitted to be considered, where applicants should provide details of their qualifications, including a CV and a personal statement. For more information on the Miller group, visit http://www.millertime.co.uk and follow us @millerlabkeele.

To submit a formal application please go to: https://www.keele.ac.uk/study/postgraduateresearch/studentships/

Please quote FNS 2021-17 on your application.

Submission: Closing date for applications 28/02/22: Applications (and interviews therefrom) will be considered on a rolling basis and the position will be considered filled once a suitable candidate has been identified.


Funding Notes

The project is funded by Riboscience at Keele University for four years - stipend and fees for UK students. Non-UK students would be required to pay the additional overseas fees themselves. Stipend at UKRI rates . Stipend for 2021/2 is £15609 per annum.

References

[1] Eastman, R. T.; Roth, J. S.; Brimacombe, K. R.; Simeonov, A.; Shen, M.; Patnaik, S.; Hall, M. D. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent. Sci. 2020, 6, 672. [2] Benkovics, T.; McIntosh, J.; Silverman, S.; Kong, J.; Maligres, P.; Itoh, T. et al. Evolving to an Ideal Synthesis of Molnupiravir, an Investigational Treatment for COVID-19. ChemRxiv. 2020, Preprint https://doi.org/10.26434/chemrxiv.13472373.v1 [3] (a) Miller, G. J. Unifying the synthesis of nucleoside analogs. Science 2020, 369, 623. (b) Guinan, M.; Benckendorff, C.; Smith, M.; Miller, G. J. Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues. Molecules 2020, 25, 2050.
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