Slack Group – Molecular Mucosal Immunology

The vast majority of our encounters with bacteria are via colonization of our mucosal surfaces, with roughly as many bacterial living in the large intestine as you have human cells in your body. These microbes contribute to health, yet we know what every one of us carries around a large burden of opportunistic pathogens in our microbiota. For example, some E. coli found in the gut can spread within us or to susceptible individuals and cause life-threatening diseases such as pyelonephritis, sepsis and neonatal meningitis.

The Slack group is dedicated to understanding how these opportunistic pathogens are controlled before they become disease-causing. We apply this knowledge to develop therapies and treatments to replace pathogens with harmless or beneficial bacteria within intact microbiomes. With this approach, we can prevent infections at source, potentially reversing the antibiotics resistance crisis by eradicating the reservoirs of resistance genes.

This group is hybrid between BIIE, ETH Zurich and the Sir William Dunn School of Pathology, Oxford.

Research Focus

To achieve our goal of preventing serious early-life bacterial infections, our research is focused across three main areas:

1. Understanding mucosal antibody induction and function

2. Understanding the role of microbial ecology and host physiology in microbiome control

3. Mucosal vaccine design and synthesis

Our work has uncovered a major mechanism by which vaccine-induced secretory antibodies in the gut can aggregate and eliminate specific bacteria, referred to as “enchained growth” (Moor et al. Nature 2017). Critically, these types of immune responses do not induce inflammation (Diard et al. Science 2017), generate strong selective pressure that drives evolution of antibody-escape variants (Diard et al. Nature Microbiology 2021) and can be used to manipulate competition between bacterial species in the gut (Lentsch et al. Science 2025).

We are combining rational vaccine design (bacterial and protein engineering), classical immunology, biophysics, computational modelling, metabolomics, and native mass spectrometry of antibody-antigen complexes to advance these concepts to a point where they can be applied clinically. The ability to rationally outcompete a pathogen with a benign bacterial strain has potentially huge implications for controlling antibiotic resistant bacterial pathogens that colonize the gut, such as E. coli, Salmonella, Klebsiella and Shigella. As these species cause disease world-wide, but high the highest morbidity and mortality in infants in low and middle-income countries, we are also focused on developing interactions that can be realistically applied in these settings.