Projektbeschreibung
CRISPR/Cas9 zur Identifizierung von Regulatoren der Geweberegeneration bei entzündlichen Darmerkrankungen
Entzündliche Darmerkrankungen sind schwere chronisch-entzündliche Erkrankungen des Verdauungstrakts, bei denen die Darmschleimhaut stark geschädigt wird. Eine therapeutische Regeneration des Darmepithels soll die Gewebeintegrität wiederherstellen und auch die Entzündungssymptomatik lindern. Das EU-finanzierte Projekt ScrIntOR untersucht daher zelluläre und molekulare Mechanismen, die an der epithelialen Regeneration beteiligt sind. Mit einem bahnbrechenden In-vitro-Organoidsystem werden Epithelzellen im regenerativen Zustand erfasst, ergänzt durch ein umfassendes Screening mittels CRISPR/Cas9, das neue Regulatoren der Darmregeneration enthüllen soll. Zudem validiert ScrIntOR wichtige Signalwege für die Darmregeneration und analysiert das Zusammenwirken molekularer Signalwege, die die Gewebeheilung unterstützen.
Ziel
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.
Wissenschaftliches Gebiet
- 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
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Aufforderung zur Vorschlagseinreichung
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
1165 Kobenhavn
Dänemark