GuT Memory
Financiado
Engineered symbionts elucidate gut T cell memory and its (dys)regulation
A detailed understanding of intestinal T cell memory is crucial for novel treatments against inflammatory bowel disease but also for efficient vaccine design. Th cells induced by the gut microbiota are important for pathogen defen...
A detailed understanding of intestinal T cell memory is crucial for novel treatments against inflammatory bowel disease but also for efficient vaccine design. Th cells induced by the gut microbiota are important for pathogen defence and tolerance, but it is unknown whether they form immunological memory characterised by long-term, antigen-independent maintenance. This has been due to the technical inability of disconnecting T cell induction from bacterial persistence in the gut.
The GuT Memory project will yield unique insights into microbiota-directed Th cell memory and its (dys)regulation through uncoupling Th cell induction from luminal persistence of the microbe.
Mutant strains of non-pathogenic gut bacteria engineered to transiently colonise germ-free mice will be combined with state-of-the-art adoptive transfer experiments to trace antigen-specific Th cells into the memory phase after their inducing bacterium has been cleared from the gut. With this, I aim to (1) elucidate how the longevity of such responses is regulated by host survival niches versus microbiota-mediated attrition. Uncovering (2) how the sequence of bacterial exposures and their microbial context shape the functional repertoire of such Th cells will demonstrate the impact of lineage flexibility on their protective versus pathogenic potential. (3) Ultimately, successive transient colonisations will provide a novel approach to dissect the physiological relevance of microbiota-specific memory Th cells for the luminal microbe, host protection, and epithelial function. These findings will aid mucosal vaccine design and indicate novel approaches to target pathogenic Th cells in chronic inflammatory disorders.
The ground-breaking nature of this proposal lies in the innovation of being able to uncouple microbiota-mediated T cell induction from luminal antigen persistence to understand how T cell maintenance is fine-tuned to promote host–microbial mutualism while avoiding aberrant inflammation.
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Duración del proyecto: 63 meses
Fecha Inicio: 2024-05-05
Fecha Fin: 2029-08-31
Fecha Fin: 2029-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-05
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG:
ERC STARTING GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
JULIUSMAXIMILIANSUNIVERSITAT WURZBURG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5