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Chemical and enzymatic tools for pathogen glycobiology


Project Description

Dual-award between The University of Manchester and The University of Melbourne.

This dual-award programme offers candidates the opportunity to apply for a project with a strong supervisory team both in Manchester and in Melbourne. A dual award is a PhD programme which leads to separate awards from two partner institutions. PhD candidates will be registered at both Manchester and Melbourne and must complete all of the requirements of the PhD programme in both the home and partner university.

PhD candidates will begin their PhD in Manchester and will then spend at least 12 months in Melbourne. The amount of time spent at Manchester and Melbourne will be dependent upon the project and candidates will work with their supervisory team in the first year to set out the structure of the project.

Project Description
In a world where resistance to antibiotics is commonplace, there is an urgent need to develop new ways to prevent or treat infectious diseases. The goal of this project is to develop and exploit a suite of enzyme tools and carbohydrate probes with which to ask questions about carbohydrate metabolism in important human pathogens, such as parasitic Leishmania and Mycobacterial species. Depending on the expertise and interests of the student, the project will provide opportunities to explore aspects of carbohydrate synthetic chemistry, enzymes in synthesis, the development and assessment of substrates and inhibitors of enzymatic processes central to pathogen metabolism and survival.

This project is a joint venture between the groups of Rob Field and Sabine Flitsch (Manchester, UK http://www.mib.ac.uk/) and Malcolm McConville and Spencer Williams (Melbourne, Australia http://www.bio21.unimelb.edu.au/). The student will initially be based in Manchester and will have the opportunity to spend 12-18 months with the Melbourne team over the course of their 3.5 years study. The team have substantial experience in carbohydrate chemistry, biochemistry and microbiology and currently host over 40 students and postdocs between them. Hence the student will be integrated into vibrant, well-resourced teams with substantial momentum in the subject area of the PhD.

Academic background of candidates:
The project would suit a student with a strong Masters level training in chemistry or biochemistry who is keen to embrace multidisciplinary research that spans the chemistry biology interface. Previous relevant laboratory experience would be a distinct advantage, although experience with carbohydrates is not essential as full training will be provided.

Contact for further Information:
Rob Field –
Sabine Flitsch –
Malcolm McConville –
Spencer Williams -

Funding Notes

Funding for the programme will include tuition fees, an annual stipend (around 15,000 for 2019/20), a research training grant and student travel to Melbourne. You will spend at least 12 months at each institution and will receive a dual PhD at the end of the 3.5 year programme.

Open to UK/EU applicants only.

The programme will commence in September 2020.

References

1] Assessment of the kinetic and chemical competence of β-1,4- and β-1,3-glucan phosphorylases inform access to new-to-nature analogues of human milk oligosaccharides, Pal Singh R, Pergolizzi G, Nepogodiev SA, de Andrade P, Kuhaudomlarp S, Field RA, ChemBioChem in press doi.org/10.1002/cbic.201900440 (2020)
2] A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites. Sernee MF, Ralton JE, Nero TL, Sobala LF, Kloehn J, Vieira-Lara MA, Cobbold SA, Stanton L, Pires DEV, Hanssen E, Males A, Ward T, Bastidas LM, van der Peet PL, Parker MW, Ascher DB, Williams SJ, Davies GJ, McConville MJ, CELL HOST & MICROBE 26(3); 385-399 (2019).
3] Applications of a highly alpha 2,6-selective pseudosialidase. Both P, Riese M, Gray CJ, Huang K, Pallister EG, Kosov I, Conway LP, Voglmeir J, Flitsch, SL, GLYCOBIOLOGY 28(5); 261-268 (2018)
4] Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing. Both P, Green AP, Gray CJ, Sardzik R, Voglmeir J, Fontana C, Austeri M, Rejzek M, Richardson D, Field RA, Widmalm G, Flitsch SL, Eyers CE, NATURE CHEMISTRY. 6(1); 65-74 (2014).
5] Synthesis, Structural Elucidation, And Biochemical Analysis of Immunoactive Glucuronosyl Diacylglycerides of Mycobacteria and Corynebacteria. Cao B, Chen X, Yamaryo-Botte Y, Richardson MB, Martin KL, Khairallah GN, Rupasinghe TWT, O'Flaherty RM, O'Hair RAJ, Ralton JE, Crellin PK, Coppel RL, McConville MJ; Williams SJ, JOURNAL OF ORGANIC CHEMISTRY 78(6); 2175-2190 (2013)

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