A human ‘mini-gut-on-a-chip’ to study microbial-epithelial cell interactions

SAEED_U20DTP

Human organoids are 3D fragments of adult tissues and ideally conserve all of the (stem) cell types and recapitulate all of the (patho)physiological processes associated with human health and disease. Although current organoid culture systems fulfill most of these criteria they suffer from being enveloped in a closed, static environment which conflicts with the in vivo situation.

Therefore, we have been developing a novel dynamic human ‘mini-gut-on-a-chip’ system that preserves access to the pseudo gut lumen for microbial co-cultures while the epithelial lining is sustained by a perfusion system analogous to peripheral blood. Mechanical contractions will also be imposed to mimic peristalsis.

The successful student will help develop the human ‘mini-gut-on-a-chip’ system and use it to investigate the molecular mechanisms and physiological consequences of microbial-epithelial cell interactions and luminal-sensing in the human gut.

Changes in the composition of the gut microflora and gut barrier function are associated with an increasing number of diseases. The student will use E. coli and Salmonella as model micro-organisms for commensal and pathogenic bacteria, and will define which microbial ligands activate which receptors on which epithelial cell types and characterise the signalling pathways that stimulate gut stem cell biology and goblet cell mucus secretion to maintain gut epithelial cell homeostasis, barrier function and gut health.

This project builds on recent successes in human gut organoid culture in synthetic hydrogel polymers and microbial co-culture. The successful applicant will be a talented researcher with an enthusiasm for biomaterials, stem cell biology and gut physiology, and will develop multidisciplinary skills in polymer chemistry, biomaterials, 3D scaffold, stem cell biology, fluorescence imaging and an understanding of the molecular basis of lumina-sensing. Research will be performed within a vibrant and dynamic environment in the laboratories of Drs Aram Saeed, Mark Williams and Gary Rowley.