Adapting the human intestinal epithelial organoid culture model for the use in paediatric and GI disease (360G-Wellcome-202483_Z_16_Z)

Inflammatory Bowel Diseases (IBD) are still not entirely understood, particularly the mechanisms that lead to their development in patients. Despite the research community's efforts little or no evidence of a genetic predisposition can be identified. Meanwhile the incidence of IBDs has been increasing, especially in western and westernised countries. Epigentics poses an interesting research target for finding the link between environmental changes and the incidence of IBDS. It has already been shown to effect gene expression in other systems and could prove key in linking our environment to the observation of the IBD phenotype. DNA methylation is one of the most widely researched epigenetic mechanisms to date, and involves the attachment of a methyl group to the 5' position on the pyrimidine ring of the nitrogenous base, Cytosine. Through increased methylation, the chromatin state is repressed and transcription is inhibited. Patients with IBDs exhibit a distinct isolated distribution of inflammation, suggesting that molecular changes have occured within the specfic gut segment. We intend to use isolated DNA and RNA from gut biopses to test the hypothesis that aberrant DNA methylation in the intestinal epithelium is either the cause and/or contributes to the observed relapsing, inflammatory phenotype in patients with IBD.