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Cellular cartography of the intestine in health and inflammation

Descripción del proyecto

Secuenciación «in situ» para mapear las interacciones celulares en la mucosa intestinal

En condiciones naturales, el epitelio intestinal es una barrera física dinámica que actúa como primera línea de defensa inmunitaria. El daño a la monocapa de células del epitelio intestinal altera la homeostasis inmunitaria del intestino y conduce a enfermedades inflamatorias intestinales (EII), como la colitis ulcerosa y la enfermedad de Crohn. Dada la creciente incidencia de las EII en las sociedades modernas, los científicos del proyecto financiado con fondos europeos GUTMAPS tienen como objetivo investigar el tejido intestinal con una resolución sin precedentes. Para ello, realizarán una secuenciación «in situ» para perfilar células individuales, mapear interacciones entre células y ayudar a comprender mejor este órgano tanto en la salud como en la enfermedad.

Objetivo

The intestinal epithelium is the first line of defence of the mucosal immune system because it acts as a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. This barrier is mainly formed by a monolayer of specialised intestinal epithelial cells (IECs) that are crucial in maintaining intestinal homeostasis. Damage to this epithelial layer can increase intestinal permeability and lead to abnormalities in interactions between IECs, stromal cells and immune cells in the underlying lamina propria thereby disturbing the intestinal immune homeostasis, all of which are a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major forms of IBD, affecting an estimated 4 million people in the United States and Europe and have a rising incidence in the developing world. Recent single cell RNA seq (scRNAseq) studies of the intestine have allowed us to understand this organ in unprecedented detail, however, such studies still require the dissociation of tissue and loss of spatial resolution. With this project, I would like to take advantage of recent advances in in-situ sequencing to study intestinal tissue in toto and by combining this with the available scRNA-seq data, generate spatial maps of the intestine (GUTMAPS). The results obtained here will allow us to look at tissue composition and cell-cell interactions with unprecedented resolution in normal and diseased mucosa.

Coordinador

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Aportación neta de la UEn
€ 187 572,48
Dirección
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Países Bajos

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Región
West-Nederland Zuid-Holland Groot-Rijnmond
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 187 572,48