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Research

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Pathogens

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Bacteriophages

Enteric bacterial pathogens (bacteria that cause intestinal disease) massively change the intestinal environment. They perturb epithelial physiology, modulate host immune responses and disrupt the intestinal microbiota. To achieve this, pathogens use a variety of virulence factors to manipulate the environment and adjust it to their own advantage. Our research questions:

  • What are the changes that occur in the intestine upon infection with an enteric pathogen?

  • How do bacterial pathogens overcome the commensal microbiota?

  • How do virulence factors promote the expansion of bacterial pathogens in the gut?

Bacteriophages, viruses that infect bacteria, are the dominant form of viruses in the intestinal microbiota. Bacteriophages can shape the gut microbiota by predation and by horizontal gene transfer. They can also modulate inflammatory processes by regulating bacterial gene expression and virulence and by directly triggering anti-viral innate immunity. Prophages, bacteriophage genomes integrated into the bacterial DNA, are common in pathogen genomes and in genomes of commensal bacteria associated with the human gut microbiome. Our research questions:

 

  • What are the mechanisms that underlie prophage induction in the intestine?

  • How does inflammation affect the intestinal virome?

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The microbiota

Balanced, diverse gut microbiota is important for proper metabolic and immune functions, and for protection against pathogens. Many pathological conditions are associated with shifts in the composition and structure of the gut microbiota. However, the mechanisms that maintain a beneficial gut microbiota during homeostasis, and the nature of their disruption during disease, remain poorly understood. Our research questions:

  • What are the mechanisms that drive dysbiosis during inflammatory disease?

  • How do commensal strains of the gut microbiota affect pathogen virulence?

  • What are the molecular mechanisms that underlie colonization resistance?

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The host

The physiology of the gastrointestinal tract and the immune system shape the intestinal microbial community, yet the precise pathways remain elusive. Inflammation dramatically affects the intestinal environment, as it disrupts host physiological functions and disturbs the structure and activity of the gut-associated microbial communities.

 

  • How do anti-bacterial mechanisms control commensal and pathogenic bacterial strains in the gut?

  • How does inflammation change the intestinal environment and the microbial landscape in the gut?

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