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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.

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

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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