Exploring the biosynthesis of a rare sugar in Clostridium difficile

Clostridioides difficile (C. difficile) is the leading cause of antibiotic-associated diarrhoea within healthcare environments worldwide. Infections by this bacterium cause significant morbidity, as well as death. First line antibiotic treatments for C. difficile infections are flawed, often damaging the gut microbiota. Antibiotic resistance is also rising, therefore there is an urgent need to explore new targets for therapeutic intervention. Hypervirulent strains of C. difficile decorate their flagella with a complex sugar chain or “glycan”, and this is required for motility and adhesion to intestinal epithelial cells. The glycan includes a rare non-mammalian sugar called L-rhamnose. The L-rhamnose biosynthetic genes are essential in C. difficile, suggesting that the pathway might be a good target for novel antimicrobials. The student will work at the interface of biology and chemistry to express the L-rhamnose biosynthetic enzymes in bacterial expression systems, and characterise each enzyme in the pathway. The student will gain experience in a range of molecular biology, biochemistry and analytical chemistry techniques such as bacterial transformation, protein expression and purification, SDS-PAGE, mass spectrometry and NMR. They will work in the interdisciplinary Fascione research group, where they will have the opportunity to present their research findings in bi-monthly group meetings. Students will need to find their own accommodation and be expected to present their findings orally at a research day in York on 08th September 2026.