Investigating host-microbial crosstalk, immunity and tissue repair at the intestinal barrier

Our group studies the gastrointestinal tract with a particular focus on host-microbiota interactions, tissue homeostasis and barrier immunity. Environmental factors, such as diet and intestinal microbiota, are important modulators of intestinal physiology yet little is known about how these cues are integrated at the cellular and molecular level. We investigate the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor capable of sensing dietary components and microbial metabolites. We and others have demonstrated that genetic deficiency in AHR is associated with compromised intestinal barrier integrity, altered microbiota composition and dysregulated host responses to pathogens and injury. Importantly, genome-wide association studies have identified AHR as susceptibility locus in inflammatory bowel disease, highlighting the relevance of this pathway to human disease.

The aim of this project is to explore the complexity and function of newly discovered AHR-dependent cell-types in the gastrointestinal tract using a variety of approaches. Firstly, you will gain experience with in vivo models of enteric infection, intestinal tissue injury and metabolic disease. Secondly, you will use single cell RNA-sequencing to generate high-resolution AHR-responsive cellular networks of distinct intestinal compartments and disease states. Thirdly, you will perform genome-wide mapping of AHR binding sites by ChIP-seq on specific cell-types within their native tissue microenvironment. Finally, you will become proficient in multiparameter flow cytometry, confocal microscopy as well as standard molecular biology techniques.

Together, your findings will provide important insights into the regulation of intestinal physiology by AHR and may facilitate the discovery of novel therapeutics for the treatment of chronic inflammatory diseases.