Impact of bacterial sialic acid metabolism on gut homeostasis

The gastrointestinal (GI) tract is colonized by a diverse community of microbes catabolizing dietary and host carbohydrates during their expansion within the gut. In particular some gut bacteria have the ability to forage on host glycans provided by the mucus layer via specific glycoside hydrolases. Alterations in mucosal carbohydrate availability impact on the composition of microbial species including enteric pathogens. We recently showed for the first time that some gut symbionts express intramolecular trans-sialidases allowing bacteria to thrive within mucosal environments by scavenging sialic acid from mucus in a form which may not be readily accessible to surrounding bacteria. The PhD project will explore the molecular basis for IT-sialidase mediated metabolism by gut bacteria and how it influences bacterial colonisation and pathogen expansion in the gut. This work will provide molecular targets to devise dietary strategies for reducing or preventing GI infection.

The student will receive expert training in anaerobic microbiology, bacterial infection, heterologous expression, carbohydrate biotransformations, separation and structural characterisation techniques (HPLC, MS- and NMR-based methods), enzymatic assays, bioinformatics and statistical analysis. There will be opportunities to collaborate with structural biologists. The techniques are well-established and there is considerable expertise in conducting research on glycobiology and gut microbiology. This interdisciplinary project will benefit from the established international network of academic and industrial collaborations of the NRP Labs in these areas of research. Training will embrace research practice and theory, management, communication (to scientific and lay audiences), teamwork, and technical writing. The student will present his/her work to internal seminars and to relevant International meetings. The possible commercial issues relating to the impact of this research on human health will be highlighted and the student will be encouraged to present his/her results to the general public.