Current projects

The Vornhagen Lab studies contextual bacteriology: how host physiology, tissue environment, resident microbial communities, bacterial genotype, and interactions between microbes shape bacterial fitness and pathogenesis.

If you are interested in working on any of these projects, please feel free to reach out to Jay!

Host physiology and functional colonization resistance

The intestinal microbiome normally creates a powerful ecological barrier against colonization by opportunistic pathogens, but this protection varies substantially among hosts and can be disrupted by disease.

We study how host metabolic state and microbial community function interact to establish or undermine colonization resistance. Using natural microbiome variation, bacterial genetics, multi-omic approaches, and experimental models of metabolic disease, we ask which environmental constraints prevent opportunistic bacteria from expanding in the gut and how those constraints change during disease.

Bacterial physiology, activity, and evolution during colonization

Bacteria encounter dramatically different environments as they move between hosts, microbial communities, and anatomical sites. We investigate how bacterial populations sense, respond to, and adapt to these environmental constraints.

Our work combines bacterial genetics with functional approaches including transcriptomics, activity-based protein profiling, and experimental evolution to identify the genes, metabolic pathways, and enzymatic activities that permit bacteria to persist within complex microbial communities.

We are particularly interested in adding time to our understanding of bacterial pathogenesis. Colonizing organisms may reside in a host for months or years, providing opportunities for both physiological adaptation and genetic evolution. By experimentally replaying colonization across different microbial communities, we ask whether ecological context drives predictable evolutionary trajectories and whether adaptation during colonization alters persistence, transmission, therapeutic susceptibility, or subsequent infection.

Ultimately, this work seeks to identify conserved bacterial dependencies that remain vulnerable across diverse host and microbial environments.

Tissue-dependent polymicrobial infection

Many infections contain more than one bacterial species, but simply finding organisms together does not tell us whether they compete, cooperate, or independently occupy the same environment.

We study when interactions between co-infecting bacteria become meaningful determinants of disease. Our work examines how tissue chemistry, host disease, bacterial genotype, and spatial organization alter the outcome of interspecies interactions.

A common goal

Across these projects, we return to three questions: What environmental constraints do bacteria experience? How do bacterial populations respond to and overcome those constraints? And can host physiology or microbial ecology be manipulated to restore protective constraints?

Our long-term goal is to develop a predictive understanding of opportunistic infection that integrates host state, microbial ecology, tissue environment, and bacterial physiology. By understanding why particular environments permit colonization or disease, we hope to identify ways to prevent infection by restoring the ecological and physiological barriers that normally keep opportunistic bacteria in check.