A high-resolution spatiotemporal map of infected cell extrusion from the human gut epithelium

• Applicant: Dr. Nora Trinks
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557544188

The project “A high-resolution spatiotemporal map of infected cell extrusion from the human gut epithelium” will focus on primary human IEC extrusion as a specialised host defence, key against invasive bacteria. Investigation of characteristic events and progression of extrusion from three gut segments are the proposals focus. For creating a spatiotemporal map, advanced microscopy techniques will be used and combined. Structural information derived from live-cell DIC imaging of infected organoid-derived epithelial monolayers will be extended with information derived from confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and possibly Expansion Microscopy (ExM) as semi-correlative approaches. Targets of interest are cell cytoskeleton components such as actin and microtubules, as well as junctional proteins like E-cadherin/ZO-1 or the microvilli cross-linker complex CDHR2/5. Those structure-giving components are expected to undergo massive changes to force single cell extrusion from an epithelial monolayer, while maintaining gut barrier function. The fate of microvilli in the early extrusion process will be addressed by high-resolution SEM. Mechanistic insights will be provided through treatment with disulfiram (DSF), a direct Gasdermin D (GSDMD) pore formation inhibitor. Furthermore, cell extrusion progression, during STm infection, will be compared to extrusion mediated by other toxic insults, like TNF-α or staurosporine. As a result, a comprehensive map summarizing key characteristics and the mechanism of IEC extrusion during STm infection is produced, predicted to highlight unique and shared extrusion features compared to other insults. This 2-year project aims to provide a deep understanding, how IEC death and extrusion operate in parallel and how they are coordinated to effectively drive pathogen clearance and maintain gut barrier function.

• DFG Programme: WBP Fellowship
• International Connection: Sweden
• Host: Dr. Mikael Sellin