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Deciphering the niche adaptations of a gut commensal involved in educating the h...

Deciphering the niche adaptations of a gut commensal involved in educating the host immune system 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 pr... ver más

31/05/2027

INSERM

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-02-17

ERC-2019-COG: ERC Consolidator Grant Scope:Objectives

I+D

Cerrada hace 6 años

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2 Participantes

INSERM

2.00M€ | Lider

BMAT LICENSING

350.00K€ | Participante

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Duración del proyecto: 87 meses Fecha Inicio: 2020-02-17
Fecha Fin: 2027-05-31

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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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