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NICHEADAPT SIGNED

Deciphering the niche adaptations of a gut commensal involved in educating the host immune system

Total Cost €

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EC-Contrib. €

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Partnership

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 NICHEADAPT project word cloud

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

exacerbate    vertebrate    maturation    immune    allowed    induction    broad    pro    sequencing    lack    structure    severity    developmental    employed    autoimmune    interaction    constraints    mass    link    unicellular    tlr5    flagellated    segmented    mediate    evolution    intimate    epithelial    pathogens    found    microscopy    remained    replicative    niche    proteins    microbiota    induces    host    bacterium    immunological    epithelium    first    overcame    postnatal    establishing    bacteria    tested    stage    resistance    generation    inflammatory    plays    activation    species    gnotobiology    particle    critical    co    driving    humans    ileal    missing    revealing    striking    integral    life    culturing    structures    consequence    transcriptomics    pathogen    disease    cell    immunostimulatory    spectrometry    cycle    signaling    sfb    pointed    stimulate    tip    vitro    iga    models    discovered    protecting    filamentous    attachment    hurdle    gut    health    fosters    surface    localized    genome    notably    microbe    poorly    techniques    th17    commensal    monocolonization    infectious    view   

Project "NICHEADAPT" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

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 France [FR]
 Total cost 1˙999˙948 €
 EC max contribution 1˙999˙948 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2021
 Duration (year-month-day) from 2021-01-01   to  2025-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙999˙948.00

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 Project objective

The gut microbiota plays an integral part in driving the postnatal maturation of the gut immune system and in protecting the host from pathogens. The commensal segmented filamentous bacteria (SFB) plays a critical role in these processes through its intimate attachment to the ileal epithelium using a unique pointed tip structure on its unicellular ‘infectious’ particle. SFB induces a broad pro-inflammatory immune activation, and notably a striking induction of IgA and Th17 cell responses, that fosters pathogen resistance but can also exacerbate disease severity in a number of autoimmune models, making SFB an important microbe in health and disease. SFB is found in many vertebrate species, including humans, and SFB monocolonization has allowed a detail study of its immunostimulatory potential. However, the unique and complex life-cycle of SFB and SFB’s interaction with the host has remained poorly understood due to a lack of in vitro culturing techniques. We recently overcame this hurdle by establishing the first in vitro SFB-host cell co-culturing system. Using this system, unicellular SFB were discovered to be flagellated and to stimulate TLR5 signaling, revealing a missing link of immunological importance in the SFB life-cycle. This important developmental stage will now be further characterized and its immunological consequence assessed using gnotobiology. State-of-the-art microscopy techniques will be employed to characterize in detail the SFB life-cycle and novel structures discovered during in vitro growth. Unicellular SFB surface proteins will be identified using mass spectrometry, localized on the bacterium and tested for their ability to mediate host cell attachment. In addition, next generation sequencing and transcriptomics will be used to assess SFB genome evolution and SFB niche constraints. Together, this work will lead to a detailed view of the SFB life-cycle and how SFB has adapted to its unique replicative niche at the epithelial surface.

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