Emma Slack

Molecular Mucosal Immunology

The mammalian large intestine contains one of the densest microbial consortia found anywhere on the planet. While some of these microbes are genuinely beneficial, synthesizing vitamin K or helping to digest dietary fibre, this is typically also home to an array of opportunistic pathogens. Our research focuses on elucidating the mechanisms by which the mucosal immune system can control the abundance and pathogenicity of these microbes.

Our current research approach aims to continuously bridge between fundamental immunology research, microbial ecology, and clinical applications. On-going projects include:

Defining how anti-bacterial intestinal IgA responses are induced: Parenterally delivered antigen tends to induce broad T and antibody responses dependent on mismatch to self and presence of adjuvant. However, the simple rules based on the presence of microbially-derived patterns and non-self antigens are not sufficient to explain immunogenicity at our mucosal surfaces. We address this challenge using reductionist systems which allow us to control the composition or the gut microbiota and the specificity of T and B cell receptors. Additionally, we employ synthetic biology concepts to design and test novel oral vaccine formulations with different combinations of covalent and non-covalent linkages between glycan and peptide antigens, as well as different adjuvants. With these tools, we aim to understand 1) the mechanisms promoting gut luminal sampling and antigen presentation in gut associated lymphoid tissues and 2) the mechanisms by which microbiota composition can influence oral vaccine efficacy.

Defining the role of capsular polysaccharides in resistance to intestinal IgA-mediated clearance of Enterobacteriaceae: In this project we characterize capsular polysaccharide structures and investigate the role of their expression on 1) the induction of intestinal IgA responses specific for surface glycan and protein structures and 2) the protective mechanisms of intestinal IgA targeting different surface glycans or protein structures. This approach makes use of neutral tagging and stochastic modelling to quantify within-host population dynamics in the presence of host immunity, and the influence of different bacterial surface glycans on this interaction. Fundamental knowledge from this project will be applied for the design of mucosal vaccines which can provide a fitness disadvantage to antimicrobial-resistant pathogens, with a view to elimination of intestinal carriage.

Selected Publications


Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide in the mouse gut depends on the resident microbiota.

Hoces, D., Greter, G., Arnoldini, M., Stäubli, M.L., Moresi, C., Sintsova, A., Berent, S., Kolinko, I., Bansept, F., Woller, A., Häfliger, J., Martens, E., Hardt, W.D., Sunagawa, S., Loverdo, C. and Slack, E.

eLife – 12: e81212.

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Circadian patterns of energy metabolism are only partially reconstituted in gnotobiotic mice.

Hoces, D., Lan, J., Wenfei, S., Geiser, T., Arnoldini, M., Nowok, S., Macpherson, A.J., Stecher, B., Zenobi, R., Hardt, W-D., Wolfrum, C. and Slack, E.*

bioRxiv – doi: https://doi.org/10.1101/2021.09.08.456534

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Resistance is futile? Mucosal immune mechanisms in the context of microbial ecology and evolution.

Slack, E. and Diard, M.

Mucosal Immunol. – 15(6): 1188-1198.

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A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants.

Diard, M., Bakkeren, E., Lentsch, V., Rocker, A., Bekele, N.A., Hoces, D., Aslani, S., Arnoldini, M., Böhi, F., Schumann-Moor, K., Adamcik, J., Piccoli, L., Lanzavecchia, A., Stadtmueller, B.M., Donohue, N., van der Woude, M.W., Hockenberry, A., Viollier, P.H., Falquet, L., Wüthrich, D., Bonfiglio, F., Loverdo, C., Egli, A., Zandomeneghi, G., Mezzenga, R., Holst, O., Meier, B.H., Hardt, W-D. and Slack, E.

Nature Microbiology – 6(7): 830-841.

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IgA and the intestinal Microbiota: The importance of being specific.

Pabst, O. and Slack, E.

Mucosal Immunol. – 13(1): 12-21.

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High-avidity IgA protects the intestine by enchaining growing bacteria.

Moor, K.,* Diard, M., Sellin, M.E., Felmy, B., Wotzka, S.Y., Toska, A., Bakkeren, E., Arnoldini, M., Bansept, F., Dal Co, A, Völler, T., Minola, A., Fernandez-Rodriguez, B., Agatic, G., Barbieri, S., Piccoli, L., Casiraghi, C., Corti, D., Lanzavecchia, A., Regoes, R.R., Loverdo, C., Stocker, R., Brumley, D.R., Hardt, W-D. and Slack, E.

Nature – 544: 498–502.

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Inflammation boosts bacteriophage transfer between Salmonella.

Diard, M., Bakkeren, E., Cornuault, J.K., Moor, K., Hausmann, A., Sellin, M.E., Loverdo, C., Aertsen, A., Ackermann, M., De Paepe, M., Slack, E. and Hardt, W-D.

Science – 355: 1211-1215,

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