York YBDTP project: The sweet side of ‘evil twin’ sugars: using chemical glycobiology tools to explore the role bacterial sialic acids play in host immune evasion by pathogens

Lead supervisor: Dr M A Fascione

Co-supervisors: Dr Nathalie Signoret - Hull York Medical School and Dr Glyn Hemsworth, University of Leeds

The student will be registered with the Department of Chemistry (University of York)

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.

The Departments of Biology and Chemistry both hold an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.

The YB DTP and the University of York are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions. 

Programme: PhD in Biological Chemistry (4 years)

How to apply

To submit your application, click on apply now. You can apply for up to 3 YBDTP projects (which can be at different universities).

We advise you to read the questions in the form before submitting your application. Inside the form there is a link to a document for you to see the questions in advance.

If you have questions about the application process, please email wrdtp@leeds.ac.uk.

If you have questions about the project you are interested in, please email the project supervisor (see project description).

How we allocate:

Shortlisting will take place shortly after the closing date and successful applicants will be notified promptly. If you're shortlisted, you'll be invited for an interview on a date to be confirmed in February 2025. You'll be notified shortly after the interview dates whether your application has been successful, placed on a reserve list or unsuccessful. If you are successful, you'll be required to confirm your intention to accept the studentship within 10 days.

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Application deadline: Monday 6th January 2025