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Organoid SIGNED

Dissecting microbiome and immune interactions in human intestinal (cancer) organoids

Total Cost €


EC-Contrib. €






 Organoid project word cloud

Explore the words cloud of the Organoid project. It provides you a very rough idea of what is the project "Organoid" about.

interactions    player    types    leans    crypt    lymphocytes    perspective    species    agonistic    subjected    regulators    chart    stem    erc    lgr5    largely    microbiome    mechanisms    gut    grow    genetically    trials    adult    tumor    organismal    patient    recombined    multiple    expanded    found    grant    mostly    rests    crc    receptors    normal    single    diseased    ligands    cells    imaging    microbial    checkpoint    colorectal    apc    identification    dissect    organs    mini    vitro    signals    spondins    ultimately    underlie    individual    intestinal    wnt    display    culture    health    effectors    tils    guts    blocking    insights    technologies    epithelium    disease    activates    crypts    cancer    tumoroids    gene    neutral    stable    healthy    bacterial    organoids    pioneered    describe    manipulation    deep    clinical    molecular    antibodies    immune    communities    exist    infiltrating    epithelial    transplanted    cultured    reductionist    allowed    cell    causes    sequencing   

Project "Organoid" data sheet

The following table provides information about the project.


Organization address
postcode: 1011 JV

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 3˙062˙438 €
 EC max contribution 3˙062˙438 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

We pioneered the essential role of Wnt signals in adult stem cells, i.e. in intestinal crypts. We also found that loss of the APC gene activates the Wnt pathway and causes colorectal cancer (CRC). We then identified a Wnt target gene, Lgr5, which allowed us to define the crypt stem cells. In a previous ERC grant based on these findings, we identified novel Lgr5 stem cells in multiple organs, and defined in vitro culture conditions to grow epithelial organoids from single Lgr5 stem cells. Crucial in this was our identification of the Wnt agonistic R-spondins as the Lgr5 ligands. Cultured 'mini-guts' display all characteristics of normal gut, can be expanded for years, transplanted, and remain genetically stable.

Here, I propose a reductionist, ‘mini-gut’-based approach to two exciting research fields that currently mostly focus at the organismal/patient level: Microbiome research leans on deep-sequencing of complex microbial communities in health and disease; and immune checkpoint research in cancer rests largely on clinical trials of checkpoint-blocking antibodies. While many insights exist into the gut microbiome and -immune system, the epithelium is often treated as a neutral player. ‘Mini-gut’ technology allows us to dissect interactions of the gut microbiome with healthy and diseased epithelium, and of Tumor-Infiltrating Lymphocytes (TILs) with CRC 'mini-guts' (tumoroids).

To this end, we will describe/study 1) All immune receptors, -regulators and -effectors in the individual epithelial cell types. 2) 'Mini-guts' recombined with individual bacterial species, 3) CRC tumoroids recombined with their cultured TILs and subjected to immune checkpoint manipulation. Using advanced molecular and imaging technologies, we will chart the molecular mechanisms that underlie the interactions from the ‘epithelial perspective’. Ultimately, this program will provide molecular detail to the effects of the microbiome and immune system on our gut, in health and disease.


year authors and title journal last update
List of publications.
2018 Inha Heo, Devanjali Dutta, Deborah A. Schaefer, Nino Iakobachvili, Benedetta Artegiani, Norman Sachs, Kim E. Boonekamp, Gregory Bowden, Antoni P. A. Hendrickx, Robert J. L. Willems, Peter J. Peters, Michael W. Riggs, Roberta O’Connor, Hans Clevers
Modelling Cryptosporidium infection in human small intestinal and lung organoids
published pages: 814-823, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0177-8
Nature Microbiology 3/7 2019-07-05

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