From bench to bedside; using patient-based assays that model the gut microbiome-host interface to aid diagnosis and inform treatment of immune dysregu

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Immune dysregulation and impaired gut mucosal barrier function are intimately linked features of two paediatric inflammatory gut disorders; namely graft-versus-host disease (GVHD) and necrotizing enterocolitis (NEC). There is growing evidence of the cross-talk between gut microbes and immune populations. Lack of gut bacterial diversity and specific anaerobic bacterial strains have been implicated in disease outcome, however, the direction of causality remains undetermined. Indeed, a better understanding of the complex interplay between gut epithelium, gut microbes and immune cells will be critical for future therapeutic advance. The overarching aim of this project is to test the hypothesis that immune cell function can be modulated by microbial "therapy". As such, this project has direct translational consequences with the potential to aid diagnosis and treatment of inflammatory gut disorders. Objectives 1. To develop an immune atlas of the paediatric peripheral blood and gut compartments, in health and disease, as an aid to diagnosis and discovery. 2. To investigate the complex interplay between gut epithelium, microbes and immune cells, using an ex vivo model of primary gut epithelium The student will develop a novel physiologically relevant model of the gut epithelial monolayer that will incorporate both strictly anaerobic "commensal" bacteria (apical surface) and immune cells (basolateral surface) on either side of the gut epithelium. The "mini gut" model is a cutting-edge technique and an invaluable tool for investigating the documented interplay between gut bacteria and immune cells in a human-based system and holds exciting potential to develop patient-based assays.