Intestinal organoids to explore ECM remodelling in Crohn’s disease
Crohn’s patients often develop fibrosis, in which the extracellular matrix (ECM) around the gut tube stiffens; but it remains unclear if ECM changes are a consequence of inflammation or if they contribute to disease pathology. This project aims to create a Crohn’s model ‘in-a-dish’ by combining synthetic hydrogels that allow for ECM remodelling with intestinal organoids differentiated from human induced pluripotent stem cells. Using proteomic and microrheological techniques, we explore how modulating peri-organoid ECM composition affects epithelial susceptibility to inflammation, providing mechanistic insights into IBD pathology and potentially facilitating the development of novel therapeutic strategies.
Bioengineering approaches to modulate neuroepithelial organoid phenotype
Untangling the physiochemical and morphological processes that control human development are important for gaining a more complete understanding of physiology and disease. The neural tube is the embryonic precursor to the central nervous system and arises from patterning driven by morphogen gradients. However, recent evidence suggests that physical cues also impact patterning in the developing neuroepithelium, but are difficult to untangle. This project aims to explore the role of physical cues in establishing patterning neuroepithelial organoids.
Advanced hydrogels to study matrix remodelling in vitro
Modelling developmental, physiological and pathological processes in human tissues requires 3D materials that can mimic the native ECM and the dynamic processes that occur with it. This project aims to create a suite of biomaterials and bioengineering tools that can provide controlled biological and biophysical cues to encapsulated cells. We create hydrogels based on PEGs, hyaluronic acid and alginates and develop tools to monitor matrix remodelling in these complex 3D systems.