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MetalloGutRepair SIGNED

Identification of a Metalloproteinase-17-mediated cellular signalling circuit in intestinal regeneration and tumorigenesis

Total Cost €

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EC-Contrib. €

0

Partnership

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 MetalloGutRepair project word cloud

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

niche    lab    cellular    constant    preliminary    caused    ex    pool    intestinal    signalling    body    cells    epithelium    muscle    repairs    spectrometry    biological    independent    infections    expertise    regulator    nutrients    stem    thrive    mediates    assigned    differentiating    stress    unbiased    largely    models    smooth    researcher    goals    cleaving    candidates    plays    injury    cell    metalloproteinases    lost    responsible    commensal    visceral    data    de    reveal    gets    pathogens    host    notably    provides    attempt    original    matrix    model    mechanical    gastrointestinal    treating    cancers    organoids    identifies    water    flora    implications    mmps    absent    first    combine    proteins    iscs    career    mmp17    differentiate    unknown    substrate    lgr5    enzymes    disease    tract    metallogutrepair    co    regain    expressed    environment    mass    combines    digestive    tumorigenesis    inflammation    regeneration    rid    hypothesize    culture    injuries    subpopulation    skills    experiments    irradiation    repair    vivo    play   

Project "MetalloGutRepair" data sheet

The following table provides information about the project.

Coordinator
NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU 

Organization address
address: HOGSKOLERINGEN 1
city: TRONDHEIM
postcode: 7491
website: www.ntnu.no

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 Norway [NO]
 Total cost 196˙400 €
 EC max contribution 196˙400 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU NO (TRONDHEIM) coordinator 196˙400.00

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 Project objective

The digestive tract has been assigned important but complex tasks. It provides our body with nutrients and water. It gets rid of pathogens while allowing the commensal flora to thrive, and it quickly repairs injuries caused by the constant mechanical and biological stress. Lgr5 intestinal stem cells (ISCs) play a crucial role in these processes, but when ISCs are lost due to injury, differentiating cells must ‘de-differentiate’ into ISCs to regain the stem cell pool. The cellular signalling processes that control these repair processes are still largely unknown. Matrix metalloproteinases (MMPs) are enzymes capable of cleaving both matrix and non-matrix proteins. My preliminary data identifies Mmp17 as a crucial regulator of inflammation-induced intestinal regeneration. Notably, Mmp17 is only expressed in a subpopulation of visceral smooth muscle cells, and thus is absent from the epithelium. I hypothesize that Mmp17 cells provide essential niche factors for repair. In addition, I propose that Mmp17 plays an important role in tumorigenesis. First, I will test the role of Mmp17 in intestinal regeneration after whole-body irradiation. My in vivo studies will be supported by an original ex vivo co-culture model, where I combine organoids and muscle cells. Next, I will test the role of Mmp17 in an established tumorigenesis model. Finally, I will attempt to identify the responsible substrate that mediates these processes, both by unbiased mass spectrometry experiments, and by focusing on likely candidates. This work will reveal a new role for muscle cells in the repair of the intestinal epithelium, and may have important implications for treating inflammation, infections and gastrointestinal cancers. MetalloGutRepair thus combines my expertise in smooth muscle cells with that of the host lab in intestinal disease models, in a research environment where I will reach my immediate goals while developing crucial skills for my long-term career as an independent researcher.

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