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Unravelling specificity of epi-metabolic regulation in mouse development

When environment of the embryo changes or when development progresses metabolic reactions are rapidly affected. These alterations to chemical reactions are coupled to epigenetic memory. However, without mechanistic data on how thi... ver más

30/11/2028

UCPH

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

KOBENHAVNS 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 2023-08-17

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2022-STG: ERC STARTING GRANTS

I+D

Cerrada hace 2 años

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1 Participantes

UCPH

1.50M€ | Lider

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Últimas noticias

01-12-2024: REDES En las últimas 48 horas el Organismo REDES ha otorgado 1337 concesiones

01-12-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

01-12-2024: AEI En las últimas 48 horas el Organismo AEI ha otorgado 23 concesiones

Duración del proyecto: 63 meses Fecha Inicio: 2023-08-17
Fecha Fin: 2028-11-30

Líder del proyecto

KOBENHAVNS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto When environment of the embryo changes or when development progresses metabolic reactions are rapidly affected. These alterations to chemical reactions are coupled to epigenetic memory. However, without mechanistic data on how this coupling occurs it is difficult to understand how normal embryogenesis can proceed. This project will elucidate how metabolic changes result in specific epigenetic outcomes and address the function of such regulation. As a model we will use mouse implantation, a process tightly linked to dramatic alterations to chromatin and transcription. We found that this is also associated with extensive metabolic rewiring and that disrupting metabolic flows results in both lineage-specific and mark-specific changes to chromatin. While multiple studies uncovered that metabolism fuels chromatin modifiers with co-factors, the fundamental biological question of how specificity is achieved remains unanswered. Here we will address this challenge by directly testing the three most likely hypotheses: 1) that metabolic reactions shuttle into the nucleus where they specifically fuel chromatin changes; 2) that chromatin-bound metabolic enzymes regulate gene expression and 3) that only specific chromatin modifiers are sensitive to metabolic changes. To address these questions, we will go beyond description as we supplement multi-omic approaches with mechanistic experiments both in vitro and in vivo. Firstly, will use perturbations of nuclear metabolic enzymes and their chromatin binding. Secondly, we will implement protein engineering to render chromatin modifiers resistant to the availability of their co-factors. By uncoupling epi-metabolic regulation, we seek not only to uncover its importance for controlling chromatin states but also the implantation developmental program. This project will form a framework of how future studies can mechanistically unravel intertwined regulatory processes and assess the role of environment and nutrition in early pregnancy.

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