Descrizione del progetto
Un organoide immuno-intestinale per lo studio della malattia infiammatoria intestinale
Modelli cellulari in vitro adeguati per simulare le malattie umane devono incorporare i diversi tipi di cellule che interagiscono nel corpo umano. Il programma ORIZZONTE dell’Unione Europea finanzia EDIOM, un progetto che mira a contribuire allo sviluppo di tali modelli. EDIOM si concentrerà sulla malattia infiammatoria intestinale (IBD, inflammatory bowel disease), un disturbo immunitario incurabile del tratto digestivo. Il ricercatore principale di EDIOM ha precedentemente creato un organoide in cui cellule immunitarie e intestinali possono essere studiate insieme ex vivo. Il sistema sarà convalidato e utilizzato per verificare le ipotesi sulle interazioni genetiche e cellulari che potrebbero essere all’origine dell’IBD sulla base dell’estrazione di dati pubblici. Nel complesso, questi esperimenti forniranno approfondimenti meccanicistici sulle cause cellulari e molecolari dell’IBD.
Obiettivo
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.
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
2333 ZA Leiden
Paesi Bassi