Food allergy affects 3-10% of children and up to 10% of adults and can cause severe allergic reactions and fatal anaphylaxis. There is currently no curative treatment for food allergy. Understanding the immune mechanisms underlying food allergy and oral tolerance could enable us to identify novel targets for definitive treatment.
Complex intestinal organoid models derived from human biopsies have been developed by us and will be used as a surrogate for human intestine to study, the interactions between intestinal epithelium, food allergens and immune cells during the establishment of normal oral tolerance or aberrant allergic response to foods. Using this innovative intestinal organoid approach blood and intestinal samples from allergic and non-allergic children being assessed for cow’s milk, egg, or peanut allergies, as part of ongoing clinical studies, will be studied through a variety of approaches.
The successful student will acquire theoretical and practical skills in cell biology (cell isolation and culture, generation of gut organoids, flow cytometry, microscopy), functional genomics (scRNAseq), and molecular immunology (RT-PCR, siRNA, lentiviral overexpression, CRISPR) as well as translational research skills in allergy and clinical immunology and bioinformatics.
Objectives for each year:
• Aim 1 (year 1): Establish intestinal organoids from children’s intestinal biopsies and determine the impact of food allergens on epithelial functions.
• Aim 2 (years 2/3): Compare intestinal epithelial functions of food allergic and non-allergic children using organoid models.
• Aim 3 (years 3/4): Assess how the immune cells respond to food allergens by co-culturing lymphocytes with intestinal organoids.
This project is suitable for a 3+1 and 4 years PhD.
