Project description
Human small intestine organoids: gut epithelial cells in inflammatory bowel disease
Inflammatory bowel disease (IBD) is characterised by inflammation of the gastrointestinal tract caused by a dysregulated immune response to gut bacterial infection. The mechanism underlying this dysregulation is not clear. However, the role of gut epithelial cells in controlling gut microbes is gaining increasing attention. With the support of the Marie Skłodowska-Curie Actions programme, the Epi-IBD project will establish an in vitro model of IBD based on human small intestine organoids composed of differentiated intestinal cells. The team will use this to study how the intestinal epithelium responds to bacterial infection in the context of IBD, evaluating both a well-known IBD genetic predisposition and novel mechanisms.
Objective
As the first line of defense against intestinal pathogens, gut epithelial cells are an essential part of the immune system. They may play an important role in immune-mediated diseases such as Inflammatory Bowel Disease (IBD). IBD is a group of disorders characterized by chronic inflammation of the gastrointestinal tract. IBD prevalence is high in Western countries (0.3% in 2018) and it is rising in newly industrialized countries.
A prevailing model is that the interplay of two factors may cause IBD. First, a genetic predisposition weakens the gut immune system and causes high susceptibility to bacterial infection. Second, pathogenic bacteria infect the gut and trigger chronic inflammation.
It is still unclear how the gut immune system may fail to repress bacterial infection in IBD. Historically, most studies have been focusing on immune cells of the hematopoietic lineage, such as macrophages and lymphocytes. However, the role of gut epithelial cells in controlling gut microbes is now gaining increasing attention. In this project, I propose to use organoids composed of differentiated intestinal cells to study how the intestinal epithelium responds to bacterial infection in the context of IBD.
I will establish an in vitro model of IBD based on human small intestine organoids. I will infect the organoids with the bacterium Adherent-Invasive Escherichia coli (AIEC) and study how the differentiated intestinal cells respond to AIEC invasion. I will both test the relevance of a well-known IBD genetic predisposition (the mutation 1007fs in Nucleotide-binding oligomerization domain 2 (Nod2)) and explore novel mechanisms underlying the immune response of gut epithelial cells using RNAseq and CRISPR base editing. My project will dissect the molecular mechanisms of IBD. In addition, it will improve our understanding of the immune response of epithelial cells, which are an under-studied component of the immune system.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesgeneticsmutation
You need to log in or register to use this function
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
1011 JV AMSTERDAM
Netherlands