Group Wetter Slack Research

The dynamic interplay between mucosal bacteria and their host

Our research iterates between the development of new methods, in vivo data collection, model generation and hypothesis refinement and testing. We are using both the murine model of non-Typhoidal Salmonellosis as well as defined microbiota colonization of germ-free mice as model systems to study host-bacterial interactions in health and disease. Example of our on-going projects are:

Evolutionary consequences of high-avidity IgA binding

We are currently investigating in detail the genetic and epigenetic changes selected for by the presence of high-avidity IgA. This will reveal whether it is possible to design "non-escapable" inactivated oral vaccines for organisms such as Salmonella species.

Oral vaccination in microbiota engineering

The ability of high-avidity IgA to alter the spatial distribution of a species, and the rate at which bound bacteria are cleared in the feces, suggests it can be used to manipulate microbiota function and efficiency. We are developing inactivated oral vaccines against major intestinal microbiota species and applying these in gnotobiotic systems to study consequences for consortium composition and metabolic efficiency.

Technology development

Whilst next generation sequencing has provided unprecedented insight into the composition of consortia containing fastidious organisms, the field is currently lacking methods that give in depth insight into the population dynamics and function of a consortium. We are therefore investing efforts into flow cytometry, gas analysis and sequencing-based approaches to quantify bacterial growth rates and activity. Our on-going collaborations with biological mathematicians is essential for accurate interpretation of these data.

Salmonella_dynamics
Diagramatic representation of the within-host population dynamics of Salmonella in the murine model of non-Typhoidal Salmonellosis.

References

1. Slack, E. et al. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325, 617-620, doi:10.1126/science.1172747 (2009).

2. Moor, K. et al. Peracetic acid treatment generates potent inactivated oral vaccines from a broad range of culturable bacterial species. Frontiers in Immunology 7, doi:10.3389/fimmu.2016.00034 (2016).

3. Moor, K. et al. Analysis of bacterial surface-specific antibodies in body fluids using bacterial flow cytometry. Nature Protocols 11, 1531-1553, doi:10.1038/nprot.2016.091 (2016).

4. Moor, K. et al. High-avidity IgA protects the intestine by enchaining growing bacteria. Nature advance online publication, doi:10.1038/nature22058external pagehttp://www.nature.com/nature/journal/vaop/ncurrent/abs/nature22058.html - supplementary-information (2017).

5. Diard, M. et al. Inflammation boosts bacteriophage transfer between Salmonella spp. Science 355, 1211-1215, doi:10.1126/science.aaf8451 (2017).

 

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