H2020Индивидуална стипендия2021–2023

ScrIntOR · Genome-wide CRISPR/Cas9 screen in intestinal organoids for identification and molecular characterization of therapeutic targets to enhance tissue regeneration

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-05-01 → 2023-04-30
Финансиране от ЕС: 207 312 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Молекулярните механизми за възстановяване на чревния епител се изследват чрез генетичен скрининг върху лабораторно отгледани органоиди. Това ще помогне за откриването на нови терапевтични мишени за подобряване на регенерацията на тъканите при пациенти с възпалителни заболявания на червата.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Genome-wide CRISPR/Cas9 screen in intestinal organoids for identification and molecular characterization of therapeutic targets to enhance tissue regeneration

Around 3 million people in Europe are affected by inflammatory bowel disease (IBD), a devastating condition characterized by chronic inflammation of the gastrointestinal tract which causes severe damage to the intestinal epithelium. Current standard treatment of IBD focuses predominantly on reducing the inflammatory burden of the intestine, a symptomatic medication without promoting the regeneration of the damaged intestinal epithelium. This is because regeneration of this tissue is still very poorly understood. It is therefore of great importance to identify the molecular mechanisms driving epithelial regeneration under ulcerative conditions and thus facilitate the development of novel pharmaceutical compounds to improve tissue recovery in IBD patients. In this project, we will combine in vitro intestinal organoid cultures with a CRISPR/Cas9 screening approach to (i) identify novel regulators of regeneration in the intestinal epithelium and (ii) decipher how this process is controlled at the molecular level. The outcome of the screen and the downstream validation will substantially enhance the current understanding of intestinal repair upon tissue damage and is likely to aid in the identification of molecular pathways that will constitute new therapeutic targets for patients suffering from IBD.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания