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The chemical glycobiology of carbohydrate metabolism


Project Description

Carbohydrates are widespread in nature and fulfil many important biological functions. However, the biology of carbohydrates is much less well explored than that of nucleic acids and proteins. There is a need for biomolecular scientists to develop new tools and techniques to advance the field, with opportunities spanning fundamental discovery through to biotechnology and biomedical applications.
Research in the glycoscience groups at the Manchester Institute of Biotechnology embrace the development and exploitation of chemical principles and tools to address questions in biology, in the broadest sense. Research interests span the contemporary challenges and opportunities presented by sustainable nutrition, renewable materials, infectious diseases and industrial biotechnology. Activities range from bacterial adhesion and infection, through plant and algal polysaccharide biochemistry and enzymology, to the development of small molecule inhibitor approaches to understand carbohydrate metabolism. Projects typically involve a mix of chemical and enzymatic synthesis, inhibitor development, protein biochemistry, structural biology, metabolomics, proteomics and transcriptomics analysis. From a biology perspective, the group works cross-Kingdom - plants, algae, animals, bacteria, viruses and parasitic protozoa – which inevitably requires collaboration to ensure relevance and impact.
We now seek a PhD student to work on understanding and exploiting the enzymes of carbohydrate metabolism. Depending on the specific skills and interest of the student, the project will focus on some aspects of synthetic chemistry, analytical biochemistry, enzymatic synthesis, and metabolic pathway elucidation.

Contact for further Information:
Professor Rob Field –
The Field group will relocate to Manchester in January 2020 - https://www.jic.ac.uk/people/rob-field/
Professor Sabine Flitsch – https://flitschlab.com/
The Field and Flitsch groups will be located in the MIB - http://www.mib.ac.uk/

Funding Notes

Applications are invited from self-funded students. For UK/EU tuition fees are £15,500 and International are £30,500 for 2019/20 academic year.

Academic background of candidates.
This project would suit a Masters-level student with a background in chemistry, biochemistry or molecular cell biology, who has an ambition to work in an interdisciplinary team that operates across the chemistry-biology interface. No previous experience with carbohydrate chemistry or biochemistry is necessary - full training will be provided and projects will be tailored to the interests and expertise of the student. However, previous research experience would be a distinct advantage.

References

• Unravelling the subtleties of the specificity of -1,3-glucan-utilising phosphorylases: GH94 vs GH 149 vs GH161. Kuhaudomlarp et al, J.
Biol. Chem., 2019, 294, 6483-6493.
• A chemical genetic screen reveals that iminosugar inhibitors of plant glucosylceramide synthase inhibit root growth in Arabidopsis and
cereals. Rugen et al, Scientific Reports, 2018, 8, Article number: 16421
• Identification of de novo KDN biosynthesis in the toxic haptophyte, Prymnesium parvum, and implications for widespread sialic acid
biosynthesis amongst microalgae. Wagstaff et al, J. Biol. Chem., 2018, 293, 16277-16290.
• Complex pectin metabolism by gut bacteria reveals novel catalytic functions. Ndeh et al, Nature, 2017, 544, 65-70.
• Discrimination of epimeric glycans and glycopeptides using ion-mobility mass spectrometry: towards a comprehensive carbohydrate
sequencing strategy. Both et al, Nature Chemistry, 2014, 6, 65-74.

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