WP2: Adhesin-mediated host cell interaction in infections

We aim to understand binding of pathogen variants to host cells, how variants manipulate host cell responses, and to develop innovative organ-on-chip models to study strain and variant adhesion/colonisation of the host. We will use a combination of in vitro assays, cell lines, human cells and tissues, and organ-on-a-chip models, to understand how pathogenic variants interact with host cells (adhesion, colonization) and manipulate their responses (cell signaling, inflammation).

There is an urgent need to develop laboratory models of humanised organs to reduce dependence on animal models in scientific research. Animal models are expensive, time-consuming, ethically problematic, and often poor predictors of human biological responses. To address this, we aim to create next-generation humanised models of the gut and vasculature using advanced organ-on-chip technology to study bacteria-host interactions. This technology enables more accurate modelling of human tissues and organ-level structures compared to traditional cell culture methods. By using organ-on-chip (OoC) systems, we can observe and control these interactions with unprecedented precision, offering new insights into the mechanisms of colonisation and infection that were previously unattainable. Gut-on-chip models will be developed at Institut Pasteur, using patients derived intestinal organoids maturated in OoC (Institut Pasteur, France) to analyse the dynamics of bacterial adhesion, colonisation and invasion. Human vasculature-on-chip models will be developed at Heriot-Watt University, Edinburgh and used to investigate mechanisms of bacterial blood infection and colonisation alongside collaborators at Lund University.