Institute of Molecular Biology

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Research Interests

Guillemin zebrafish gut The gut microbiota of a zebrafish larva. Bacteria are in red, nuclei are in blue, and fish tissue is in green.

All animals are complex systems of interacting host and microbial cells. In the Guillemin lab, we strive to understand how hosts and their associated microbial communities shape each other. We use genetically tractable and microbiologically manipulable models systems including zebrafish and fruit flies. We explore the reciprocal impacts of microbial communities on their hosts and host environments on resident microbiota during development and in the context of disease. We perform experiments using gnotobiotic animals with defined microbial associations to uncover the causal relationships in these reciprocal interactions and to understand their mechanisms. We investigate host-microbe systems with scalable complexity, from germ-free and mono-associated animals to conventionally reared animals with their full complement of microbes. From these investigations we hope to understand the principles by which complex host-microbe systems functions and to learn how they can be manipulated to promote the health of systems like ourselves.

Microbial impacts on intestinal development

We have found that resident bacteria play important roles in the maturation of the zebrafish intestine, including promoting intestinal epithelial cell proliferation and recruiting innate immune cells in the gut. Many of these effects of the microbiota are conserved across animal species. We study the molecular mechanisms by which bacteria signal to the host to promote these changes, and the molecular pathways through which the host perceives and responds to these signals. We also investigate how host-microbe interactions can influence disease states, such as excess cell proliferation (cancer) or immune cells (inflammatory diseases).
Guillemin cell proliferation in germ-free zebrafish Cell proliferation in the epithelium of conventionally reared (A) and germ-free (B) zebrafish larvae.

Bacterial strategies for colonizing the host

We study how host-associated bacteria explore and establish residency in the environment of host tissues. We use live imaging to investigate the dynamics of bacterial colonization of the zebrafish intestine and genetic approaches to identify bacterial colonization strategies. One such strategy is chemotaxis, which we study in the gastric bacterium Helicobacter pylori that senses its extreme chemical environment with a limited repertoire of chemoreceptors. Our analysis of the structure and biochemistry of the chemoreceptor TlpB has revealed a novel pH sensing mechanism involving a urea cofactor.
Guillemin crystal structure of tlpb Structure of Helicobacter pylori chemoreceptor TlpB periplasmic domain dimer with urea molecules in pink.

Assembly of host-associated microbial communities

We investigate how microbial communities assemble in and on hosts and how these communities change during host development and disease. We survey complex, naturally assembled communities to discern the contributions of host, environmental, and stochastic processes on assembly. We also study simple, artificially constructed communities in gnotobiotic animals to understand the assembly principles that would allow us to engineer or manipulate more complex host-microbe systems.
Guillemin lab host-bacterial interaction diagram Bacterial-bacterial and bacterial-host interactions in a simple three member bacterial community in gnotobiotic zebrafish

Recent publications

(pulled from pubmed)