Molecular virulence mechanisms of IBD-associated intestinal pathobionts

Coco Duizer

The intestinal microbiota is believed to play a key role in the pathogenesis of inflammatory bowel disease. Each person's microbiota consists of 100-200 different bacterial species that vary greatly between individuals. However, studies in mouse models of disease suggest that many disorders are driven by a limited number of ‘pathogenic’ commensals, called pathobionts. These pathobionts often live within the intestinal mucus layer in close proximity or attached to intestinal epithelial cells. The interactions of this pathogenic subset of the microbiota with the host epithelium and immune system are still mostly unclear but believed to dramatically impact on health. The focus of this research project is therefore to reveal and characterize the molecular virulence mechanisms of IBD-associated intestinal pathobionts in the intestinal tract. Various ‘model’ pathobionts will be studies, one of which is the Gram-negative anaerobic bacterium Bacteroides fragilis.

Anaerobic microbiota culturomics, CRISPR/Cas9-mediated gene editing, bacterial mutagenesis, intestinal organoid cultures, high-throughput ligand-receptor identification, NF-kB luciferase and NF-kB-GFP reporter assays, cell culture, molecular microbiology