Project description
An immune-intestinal organoid for studying IBD
Adequate in vitro cell models for mimicking human diseases need to incorporate the different cell types that interact in the human body. The European Union HORIZON scheme is funding EDIOM, a project aiming to contribute to the development of such models. EDIOM will focus on inflammatory bowel disease (IBD), an incurable immune disorder of the digestive tract. EDIOM’s principal investigator previously established an organoid where immune and intestine cells can be studied together ex vivo. The system will be validated and used to test hypotheses on genes and cell interactions that may underlie IBD based on public data mining. Altogether, these experiments will provide mechanistic insights into the cellular and molecular causes of IBD.
Objective
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.
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
2333 ZA Leiden
Netherlands