In vitro modelling of matrix cues in Inflammatory Bowel Disease

To establish an IBD-like phenotype with the human intestinal organoids and identify novel matrix targets that can be exploited to treat IBD.

- Identify a combination of hydrogel stiffness, degradability, and adhesive ligand concentrations that in combination with appropriate exogenous cytokines lead to encapsulated hIO taking on IBD-like phenotypic characteristics (IBD-in-a-dish).
- To accomplish this we will be treating organoids with matrix remodellers and other inflammatory cytokines (TGF-b, IFN-y, TNF-a and Oncostatin M). We will identify concentrations of cytokines added to media to stimulate the IBD-like phenotype.
- Using RNAsequencing and SILAC-based proteomics on the hIO based IBD model to validate known gene/matrix components that are regulated in IBD and identify novel targets that could be exploited therapeutically to treat IBD.
- If possible we will use iPS cells derived from IBD-patients to hIO models representative of patient tissue

Incorporate newly identified targets (peptides/proteoglycans) into the established hydrogel model in the lab and identify changes to organoid phenotype.
- This will involve peptide/proteoglycan design to enable crosslinking with the established polymer-peptide designs.
- We will then characterise changes to organoid phenotype using imaging and PCR
- We will also characterise changes to stromal populations that drive changes to disease phenotype