Summary
This project aims to study the biomimetic interactions between human-adapted bacterial pathogens (H. pylori and Salmonella Typhi) and the gastrointestinal epithelium using novel organoid platforms to understand colonization, invasion, and immune responses, ultimately identifying new therapeutic targets.
What they want
The project will investigate Helicobacter pylori and Salmonella enterica serovar Typhi, major human pathogens causing gastric cancer and typhoid fever, respectively, which are becoming difficult to treat due to antibiotic resistance. The research will leverage novel biomimetic platforms of human-derived gastric and intestinal organoids, including methods to reverse polarity and control differentiation of 3D epithelial organoids, induce differentiation of intestinal microfold (M) cells, and use air-liquid interface culture to preserve the mucosal immune system. These platforms will be used to define bacterial colonization niches, elucidate invasion and intracellular replication sites, and understand secondary immune responses and feedback on the epithelium.
Deliverables
- Identification of new pathways that could serve as novel targets for decolonization, therapeutics, and vaccine strategies
Technical requirements
- Biomimetic platforms of human-derived gastric and intestinal organoids
- Method to reverse the polarity and control the differentiation of three-dimensional epithelial organoids in suspension to expose the apical surface for infection studies
- Method to induce differentiation of intestinal microfold (M) cells
- Air-liquid interface culture method to preserve the endogenous mucosal immune system
