Completed Chemistry Cells, Biochemistry & Physiology

Expediting glycosaminoglycan synthesis: expanding frontiers for carbohydrate chemical biology

Funder UKRI
Recipient organisation Keele University
Funding £593K
Period Feb 2025 — Sept 2025

In plain English

AI plain-English summary

Carbohydrates that coat every cell in the human body are notoriously difficult to synthesise in the lab, and this project aims to build them quickly and cleanly using a continuous-flow system of enzymes. These sugar-based molecules—called glycosaminoglycans—sit on cell surfaces and orchestrate a huge range of biological processes, from inflammation to cell growth. But studying them has been held back by the sheer difficulty of making them. Current chemical synthesis is slow, wasteful, and hard to control. This research tackles that bottleneck by combining flow biocatalysis with traditional organic chemistry to produce sugar nucleotides—the building blocks cells use to assemble these carbohydrates—in a reproducible, automated way. The project also explores a novel prodrug strategy that links these sugar nucleotides to nucleoside analogues, potentially opening new routes for therapeutic design. If successful, the work will give biologists a reliable supply of complex carbohydrates that are currently hard to obtain. That could accelerate fundamental research into how these molecules drive disease, and eventually feed into the design of new drugs. The field is growing rapidly worldwide but remains underrepresented in UK science, so this fellowship renewal helps close that gap.

View original technical description
This UKRI Fellowship renewal will continue to support my development of new scientific expertise at Keele University which interfaces chemistry and biology. The overarching goal of the research is to establish efficient technologies to provide biologically important carbohydrates. Such biomolecules are positioned to modulate or mediate a huge variety of biological processes and as a result there is a sustained interest from the scientific community around the synthesis of carbohydrate structures. I will harness flow biocatalysis to enable controlled and reproducible production of the building blocks essential to carbohydrate biosynthesis, sugar nucleotides. Secondly, I seek to expand the frontier of glycoconjugate chemical biology through exploration of a novel prodrug approach, combining sugar nucleotide donors and nucleoside analogues. In undertaking this research, I will adopt a multidisciplinary approach consisting of a fusion between traditional organic chemistry, biocatalysis, the evolving field of synthesis automation, and the innovative field of chemoenzymatic synthesis. This combination will facilitate the development of a faster and greener approach to explore biologically relevant carbohydrates. This is a rapidly evolving worldwide field which is currently underrepresented in UK science. The important materials provided by the technology and knowledge developed during this Fellowship renewal will be used to probe underpinning carbohydrate biology connected to disease and aid in the design and development of new therapeutic strategies.

View the original record at the funder ↗

Researchers

Gavin Miller (Principal Investigator)

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Original classification

Fellowship

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