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ProFITGut

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Proteome-wide Functional Interrogation and Modulation of Gut Microbiome Species

The gut microbiome plays a key role in human health. Genomics approaches excel at cataloguing species composition, and associating imbalances with disease. Yet, as we are oblivious to the function of a large proportion of proteins... ver más

30/04/2028

UMEA UNIVERSITET

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

UMEA UNIVERSITET 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 2022-12-16

ERC-2022-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 2 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UMEA UNIVERSITET

1.50M€ | Lider

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Duración del proyecto: 64 meses Fecha Inicio: 2022-12-16
Fecha Fin: 2028-04-30

Líder del proyecto

UMEA UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto The gut microbiome plays a key role in human health. Genomics approaches excel at cataloguing species composition, and associating imbalances with disease. Yet, as we are oblivious to the function of a large proportion of proteins of these organisms, we are limited in our understanding of the molecular mechanisms that drive disease or promote health. In this groundbreaking project we will systematically identify the function and interactions of proteins of microbiome species, deliver compounds to modulate them, and develop strategies to rationally manipulate microbiome composition. We will use a scalable systems biology approach based on high-throughput proteomics, using more than 100 drugs to perturb the proteome of a panel of 38 prevalent and phylogenetically diverse bacterial species that colonize the human gut. Proteins involved in the same biological process have coordinated changes in their levels across perturbations, allowing us to infer function based on annotated proteins. We will further assess which proteins are likely to physically interact as they co-aggregate upon heat-induced denaturation, leading to a map of the functional protein network of these species. We will then identify the mechanisms of action and resistance of the used drugs by using thermal proteome profiling, and by measuring intracellular drug concentrations. This will allow us to identify species that encode the target, but no resistance elements, so we can use the information to specifically deplete disease-associated species from microbial communities. These strategies extend beyond the strains studied in this project, as homologs of these proteins can be identified solely from genome sequences. Overall, this project paves the way for the microbiome field to move from associations to targetable mechanisms, with a vision to design therapies with reduced side effects to restore the microbiome to a healthy state.

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