DC7: Impact of microenvironment on colonisation and virulence of enteric bacteria

The PhD student will work on the impact of the microenvironment of the human gut on colonisation and virulence of enteric bacterial pathogens (EHEC). In this project you will use a highly physiological human colon model, combining patient-derived colonic organoids with organ-on-chip (OoC) and enabling to modulate the key gut environmental cues: mechanical stimulation (peristalsis and shear stress) and microbiota metabolites. Using several EHEC strains based on their differences in adhesins or Type IV pili, you will help to characterize the colonization, adhesion of these variants, and the consequence of the gut environmental cues on the EHEC virulence.

The work is in close collaboration with other groups in the network interested in host cell receptors, and in anti-adhesion drug development. The position thus offers the opportunity of internships with both academic and industrial partners.

Methods will include the generation of human colonic organoids, barrier maturation in OoC, infection assays in OoC modulating mechanical forces and microbiota metabolites, live and fixed imaging quantifying the bacterial adhesion and colonization, CFU counting, barrier leakage assays, immunofluorescence and RTqPCR analysing the downstream impact of infections on the colonic barriers.