01 · Research
Three lines of inquiry,  one interface.
Overview We build mechanistic, often quantitative pictures of how the immune system and the microbiota shape each other — and turn them into interventions that work in the field, the clinic and the barn.

Neutral-genetic barcodes

Project 01

Within-host dynamics of gut commensals

Most pictures of the gut microbiota come from sequencing or selective culture — useful for semi-quantitative snapshots, but blind to the parameters that actually govern a community: the availability of niches for incoming commensals, capacity for growth, and rate of clearance from the gut lumen.

We combine neutral-genetic tagging with mathematical models to reveal these dynamics inside the host. Using barcoded strains of the human commensal  Bacteroides thetaiotaomicron , we probe colonization potential against an established microbiota and the capacity to overcome acute challenges — clarifying the mechanisms that drive shifts in microbiota composition in health and disease.

Project 02

Next-generation oral vaccines

Recombinant vaccines against protein antigens are safe and easy to produce — but the surface of many bacterial pathogens is densely covered by complex carbohydrates, and targeting those glycans is the most effective way to prevent bacterial disease. Glycans are poorly immunogenic alone, so glycoconjugate vaccines link them to a carrier; today that production is a tedious, expensive multi-step process.

Bacterial glycoprotein engineering condenses this to a single step, linking the desired carbohydrate to a safe, self-assembling, highly immunogenic virus-like particle — at a fraction of the price. We pair this with vaccination routes that follow the route of infection, and with  evolutionary trap vaccines that force pathogens into a costly trade-off, typically losing virulence or outer-membrane robustness.
Glycoconjugate VLPs Oral delivery Evolutionary trap vaccines AMR control

Glycoconjugate render

Host physiology gradient

Project 03

Cross-talk between host physiology, diet & microbiota

Bulk descriptions of faecal communities make causal links hard to establish — they are one-off measurements of an intricate interplay between thousands of species and their host, and the microbiota varies in space along the intestine as well as in time.

We use a gnotobiotic mouse model with a simplified microbiota that recapitulates major functions of the full system, accounting for the variable physiology of the intestine — pH, bile salts, bicarbonate, osmolarity, flow — and the metabolites the microbiota secretes back. Controlled in vitro assays, in vivo data and mathematical modelling combine into a dynamic framework for hypothesis generation, with a clear path toward treating microbiota-related disease.

Funding · Swiss National Science Foundation

Collaborators

R. Zenobi · D-CHAB ETH C. Magnabosco · D-ERDW ETH M. Ackermann / A. Hockenberry · Eawag Y. Zhang · Rhode Island G. Liebisch · Regensburg

Project 04 · Botnar Centre for Child Health

Precision microbiota engineering for child health

From shortly after birth, the large intestine is colonized by billions of bacteria. We are only beginning to understand how they influence child health — yet current studies support causal roles in diseases as diverse as allergy and autism, and we still have no accurate way to "fix" the microbiota.

We are developing two tool-sets: one to replace a "bad" bacterial species with a desirable one using intestinal antibodies, and one to target individual genes in the microbiota using CRISPR-Cas directly in the gut. We begin with the most serious diseases of newborns — inborn errors of metabolism, neonatal sepsis and necrotizing enterocolitis — where mortality is high and treatment options are limited.

Intestinal-antibody strain replacement In-gut CRISPR-Cas Novel medical imaging
Project at the BRCCH 

Colony plate, OMM¹²

Epithelium, confocal

Project 05 · Hausmann subgroup

Epithelium–microbiota crosstalk

The intestinal mucosa is the barrier between our bodies and the outside world — permeable to essential nutrients, yet protective against microbial translocation. A tight balance between epithelium, immune cells and the luminal microbiota maintains homeostasis; when it breaks, the result can be infection, metabolic disorder or chronic inflammation such as inflammatory bowel disease.

The Hausmann group focuses on the epithelium itself — in direct contact with the microbiota, yet poorly understood at the molecular level. Using gnotobiotic mice, organoids combined with anaerobic culture, single-cell omics and bioengineering, we characterize the impact of commensal microbes on epithelial barrier function across mouse and human.

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