Sugars, or glycans as they are more commonly known, are the most abundant biomolecules on earth and play essential roles in a myriad of biological processes including energy storage, cell-cell recognition and the immunological response. The ubiquitous ‘sialic acid’ sugar Neu5Ac is present on the surface of all human cells and is therefore well studied, but similar bacterial sialic acids which mimic Neu5Ac are present on a range of bacteria and poorly understood in comparison. These bacterial ‘evil twins’ are highly prevalent on the surface of a number of bacterial gastric pathogens such as C. jejuni and H. pylori, and it is now clear that presentation is important for virulence. Recent evidence suggests that this bacterial glycosylation may be important for interaction with human cells, potentially dampening the immune response and effectively ‘camouflaging’ the bacteria from the host immune system by mimicry of Neu5Ac. As capacity to evade the immune response is an established key factor in the ability of pathogenic bacteria to colonize the host, bacterial sialic acid glycosylation is a bona fide target for therapeutic intervention.

Building on recent work in the Fascione Lab (Nat. Commun., 2024, 15, article number: 7925; Angew. Chem. Int. Ed., 2024, 63 (15), e202318523; JACS Au, 2024, 4 (6), 2122-2129), in this project we aim to synthesise a range of bacterial sialic acids using a combination of synthetic carbohydrate chemistry and enzymology, to help dissect the crucial interactions between bacterial sialic acids and human sialic acid binding proteins. This interdisciplinary glycoscience project will combine expertise in chemistry, immunology and structural biology to explore the molecular interactions underpinning glycan-protein binding.

The project would be suitable for a candidate with expertise in glycoscience, and/or chemical biology/biochemistry, and a willingness to train in new interdisciplinary techniques including cell and structural biology.