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AI-2 Prodrugs

Financiado

Development of new AI-2 prodrugs and chemical probes to study the microbiota of...

Development of new AI-2 prodrugs and chemical probes to study the microbiota of the mammalian gastro-intestinal tract Quorum sensing allows bacteria to synchronise and regulate their behaviours. Autoinducer-2 (AI-2) is a particularly relevant signaling molecule able to promote inter-species communication. In the mammalian gut microbiota, a therap... ver más

31/05/2024

UNL

157K€

Presupuesto del proyecto: 157K€

Líder del proyecto

UNIVERSIDADE NOVA DE LISBOA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-31

HORIZON-WIDERA-2022-TALENTS-02-01: Fostering balanced brain circulatio... ExpectedOutcome:This action builds on the MSCA Postdoctoral Fellowships 2021 action (HORIZON-MSCA-PF...

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Cerrada hace 3 años

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UNL

156.78K€ | Lider

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Duración del proyecto: 23 meses Fecha Inicio: 2022-06-03
Fecha Fin: 2024-05-31

Líder del proyecto

UNIVERSIDADE NOVA DE LISBOA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 157K€

Descripción del proyecto Quorum sensing allows bacteria to synchronise and regulate their behaviours. Autoinducer-2 (AI-2) is a particularly relevant signaling molecule able to promote inter-species communication. In the mammalian gut microbiota, a therapeutically relevant niche, interference of AI-2-mediated signaling has been shown to influence the balance of the major phyla after antibiotic treatment. Still, the mechanisms involved in this process are not known. We propose to establish novel chemical and structural based approaches to decipher the mechanisms involved in the response of the gut microbiota to AI-2 and identify mechanisms that promote beneficial responses by the symbionts while inhibiting virulence in gut pathogens. For this, we will construct chemical tools that will function as AI-2 prodrugs to orally deliver intact AI-2 to the gut. AI-2 is a highly functionalised molecule, very reactive and unstable at high concentrations, thus a prodrug strategy will protect AI-2 until its release in the gut. To gain a molecular understanding involved in response to AI-2 we will identify AI-2 sensing mechanism (receptors) in commensal and pathogenic members of the microbiota belonging to the Clostridiaceae. For that, new AI-2 fluorescent probes will be designed and synthesised. The Clostridiaceae family are relevant members in the mammalian gut. These organisms include both beneficial as well as pathogenic members and we want to identify strategies to promote the beneficial response while inhibiting the pathogenic ones to promote a healthy microbiota community. Our hypothesis is that synthetic AI-2 can help in the recovery of a healthy bacterial phyla ratio after a distress, like antibiotic treatment.

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