Description du projet
Un organoïde immuno-intestinal pour l’étude de la MICI
Les modèles cellulaires in vitro imitant les maladies humaines doivent intégrer les différents types de cellules qui interagissent dans le corps humain. Le programme HORIZON de l’Union européenne finance EDIOM, un projet visant à contribuer au développement de tels modèles. EDIOM se concentrera sur la maladie inflammatoire chronique de l’intestin (MICI), un trouble immunitaire incurable du tube digestif. Le chercheur principal d’EDIOM a précédemment créé un organoïde au sein duquel les cellules immunitaires et intestinales peuvent être étudiées ensemble ex vivo. Le système sera validé et utilisé pour tester diverses hypothèses sur les gènes et les interactions cellulaires qui pourraient être à l’origine de la MICI, sur la base de l’exploration des données publiques. Ces expériences permettront de mieux comprendre les causes cellulaires et moléculaires de la MICI.
Objectif
Inflammatory Bowel Disease (IBD) is a collective term for bowel diseases caused by undesired immune reactions and can currently not be cured. To develop adequate treatments for IBD, we need to understand the nature and cause(s) of the pathogenic immune responses observed.
To identify mechanisms driving IBD in humans, we need apart from diagnostic correlative studies, adequate in vitro cell models that realistically recapitulate the in vivo situation and allow for intervention studies. Thus far, in vitro models that incorporate next to intestinal epithelium also supportive stroma and immune cells are lacking. In my PhD studies, I generated a map of the IBD-associated immune cell network by single-cell analyses of healthy and IBD patient samples. In my postdoctoral work, I have developed an Air Liquid Interphase (ALI) intestinal organoid platform derived from human samples that supports tissue-resident immune cells.
In this project, I aim to identify cellular and molecular networks driving IBD by diagnostic and intervention studies in intestinal ALI organoids.
For this purpose, I will: 1) Validate ALI intestinal organoids as accurate ex vivo model by analyzing their immune cell composition and functionality in spatial context; and 2) aligning this with the in vivo situation by data mining of public single-cell RNA-seq of inflamed intestines. 3) Integrate datasets generated in 1-2) to reveal cellular and molecular immune cell interactions associated with IBD; and 4) Implicate interactions identified under 3) in driving IBD by molecularly targeted interventions in ALI organoids. The proposed work will take place at host institute Leiden Univ. Medical Center, with a 4-month secondment phase at Technical Univ. Delft.
This project is expected to deliver insight into immunological mechanisms driving IBD and clinically translatable therapeutic interventions, by mechanistic studies in a novel in vitro system mimicking the in vivo cellular environment of human IBDs.
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Appel à propositions
(s’ouvre dans une nouvelle fenêtre) HORIZON-MSCA-2022-PF-01
Voir d’autres projets de cet appelRégime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
2333 ZA Leiden
Pays-Bas