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DynaTrans

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Transcription in 4D: the dynamic interplay between chromatin architecture and ge...

Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos During mammalian embryogenesis, key events involving DNA and regulatory molecules over seconds and nanometers affect and are affected by, a major reorganization of the genetic material in the nucleus over hours and micrometers. Ho... ver más

30/04/2030

10M€

Presupuesto del proyecto: 10M€

Líder del proyecto

INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 3 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-12-15

ERC-2023-SyG: ERC Synergy Grants Objective:The aim is to provide support for a small group of two to four Principal Investigators to...

I+D

Cerrada hace 2 años

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3 Participantes

4.06M€ | Lider

IST AUSTRIA

2.12M€ | Participante

COLLEGE DE FRANCE

3.37M€ | Participante

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Duración del proyecto: 76 meses Fecha Inicio: 2023-12-15
Fecha Fin: 2030-04-30

Líder del proyecto

INSTITUT PASTEUR No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 10M€

Descripción del proyecto During mammalian embryogenesis, key events involving DNA and regulatory molecules over seconds and nanometers affect and are affected by, a major reorganization of the genetic material in the nucleus over hours and micrometers. How these scales are spanned and integrated into the course of development remains a major unresolved challenge. Progress in this quest is difficult, either because current model systems suffer from severe technical limitations or because existing analytical approaches probe individual spatial or temporal scales thus ignoring their evolving interactions. Traditional live imaging lacks the spatial resolution to accurately delineate chromosome organization at the scale of genes, while bulk molecular assays are ill-suited for studying development over time. Here, we propose a multi-disciplinary approach to the dynamics of developmental gene regulation to understand the details of the underlying mechanisms and their deployment over time. We combine and apply optical, molecular-genomic, and theoretical tools to recently available mammalian pseudo-embryos, allowing unprecedented precision in developmental staging, a large amount of material, and easy optical access. By focusing on select gene loci we track transcriptional activation and the interactions of distal DNA elements in real-time along with the associated chromatin dynamics using interaction profiles. Our datasets are iteratively distilled into mathematical models of increasing scope, converging towards an integrative dynamic polymer model that simultaneously captures long-timescale chromatin rearrangements as well as short-timescale motions of genetic regulatory elements and transcriptional activity. We then challenge these models via genome editing and temporally defined interventions by building light-controlled tools to affect the chromosome landscape. This project aims to reshape our view of how genes are regulated during mammalian development.

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