Combatting Salmonella infection in the gut with sialic acid derivatives

This PhD studentship provides an exciting opportunity for the successful candidate to address fundamental questions on the role of mucin-derived glycans on Salmonella infection in the gut.

The mucus layer in the intestine represents an important line of defence against bacterial infections such as Salmonella. Sialic acid is an abundant sugar residue found in terminal locations of mucin glycan chains and a key target of gut bacteria inhabiting the mucus niche. In this PhD project, the student will use in vitro and in vivo approaches including organ-on-chip technology to investigate the role of sialic acid derivatives in limiting pathogen infection.

The PhD student will join a large and dynamic multidisciplinary team at the Quadram Institute Bioscience and receive mentoring and training in relevant experimental models and state-of-the art analytical tools. Through this PhD studentship, the student will acquire expertise in molecular microbiology, glycobiology, cell biology, bioinformatics and in vivo skills.

The student will benefit from the established network of international collaborations of the host Labs in this research area. Training will embrace research practice and theory, management, communication (to scientific and lay audiences), intellectual property, teamwork and technical writing. The student will present his/her work to internal seminars and to relevant microbiology international meetings. The student will be encouraged to participate into outreach activities and innovative competitions.

References

Bell A, Severi E, Owen CD, Latousakis D, Juge N. Biochemical and structural basis of sialic acid utilization by gut microbes. J Biol Chem. 2023 299(3):102989. doi: 10.1016/j.jbc.2023.102989

Tanner JR, Kingsley RA. Evolution of Salmonella within Hosts. Trends Microbiol. 2018 26(12):986-998. doi: 10.1016/j.tim.2018.06.001.

Bell A, Severi E, Lee M, Monaco S, Latousakis D, Angulo J, Thomas GH, Naismith JH, Juge N. Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria. J Biol Chem. 2020 295(40):13724-13736. doi: 10.1074/jbc.RA120.014454.

Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC, Gopinath S, Naidu N, Choudhury B, Weimer BC, Monack DM, Sonnenburg JL. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature. 2013 502(7469):96-9. doi: 10.1038/nature12503.

Bell A, Brunt J, Crost E, Vaux L, Nepravishta R, Owen CD, Latousakis D, Xiao A, Li W, Chen X, Walsh MA, Claesen J, Angulo J, Thomas GH, Juge N. Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut. Nat Microbiol. 2019 4(12):2393-2404.