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Organoid SIGNED

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

Total Cost €

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EC-Contrib. €

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Partnership

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 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.

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

Project "Organoid" data sheet

The following table provides information about the project.

Coordinator
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW 

Organization address
address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
city: AMSTERDAM
postcode: 1011 JV
website: www.knaw.nl

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

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW NL (AMSTERDAM) coordinator 3˙062˙438.00

Map

 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.

 Publications

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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