Description du projet
Criblage par CRISPR/Cas9 pour identifier les régulateurs de la régénération tissulaire dans les maladies inflammatoires de l’intestin
Les maladies inflammatoires chroniques de l’intestin sont une affection inflammatoire chronique dévastatrice du tube digestif caractérisée par des lésions graves de l’épithélium intestinal. Les stratégies thérapeutiques doivent favoriser la réparation épithéliale pour restaurer l’intégrité des tissus en plus de soulager les symptômes de l’inflammation. Le projet ScrIntOR, financé par l’UE, vise à élucider les mécanismes cellulaires et moléculaires impliqués dans la régénération épithéliale. L’étude utilisera un système unique d’organoïdes in vitro qui capture les cellules épithéliales dans un état de régénération en combinaison avec un criblage par CRISPR/Cas9 à grande échelle pour identifier de nouveaux régulateurs de la régénération intestinale. En outre, ScrIntOR validera les voies clés de la réparation intestinale et disséquera l’interaction des voies moléculaires qui orchestrent la guérison des tissus.
Objectif
Around 3 million people in Europe are affected by inflammatory bowel disease (IBD), a devastating condition characterized by chronic inflammation of the digestive tract causing severe damage to the intestinal epithelium. Current medication strategies aim to relieve symptoms by reducing the inflammatory burden without promoting epithelial repair to restore tissue integrity. It is therefore of great importance to enhance the current understanding of intestinal regeneration and thus facilitate the development of novel pharmaceutical compounds to improve tissue recovery in IBD patients. However so far, only few regulators of intestinal regeneration with quite distinct cellular functions have been identified, suggesting an interplay of various molecular pathways that orchestrate intestinal repair. This therefore raises the question of which cellular and molecular mechanisms safeguard epithelial regeneration. To address this issue, I will combine a unique in vitro organoid system, developed in the host lab that captures epithelial cells in a regenerative state, with my expertise in large-scale screening approaches to: (1) perform an unbiased genome-wide CRISPR/Cas9 screen to identify novel regulators of intestinal regeneration, (2) validate essential pathways in intestinal repair in vitro and in vivo, and (3) dissect the molecular events coordinating tissue healing. The outcome of this project will on one hand provide a comprehensive list of factors and their molecular function controlling this cellular process and on the other hand uncover novel druggable pathways in IBD to enhance the regenerative capacity of the intestinal epithelium. Executing this MSCA fellowship proposal will equip me with expert knowledge in epithelial biology and associated pathologies, cutting-edge technologies and an essential set of transferable skills, which all together will ensure my successful establishment as an independent group leader in the field of regenerative stem cell biology.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- natural sciencesbiological sciencescell biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesbasic medicinepathology
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1165 Kobenhavn
Danemark