Innovating Works

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Learning from the past linking ancestral epigenetic states to current cellular...
Learning from the past linking ancestral epigenetic states to current cellular fates with single cell multi omic approaches The establishment of cell type-specific transcriptional programs involves many interconnected regulatory mechanisms acting on different genomic scales. To dissect this multi-layered control of gene expression in detail, I will dev... The establishment of cell type-specific transcriptional programs involves many interconnected regulatory mechanisms acting on different genomic scales. To dissect this multi-layered control of gene expression in detail, I will develop methods that a) measure multiple cellular outputs in single cells, and b) obtain that information in a time-resolved manner. This proposal outlines my approach to study early mouse development at numerous levels, including (but not limited to) transcription, chromatin context, and nuclear organization. In doing so, I expect to shed light on the mechanism behind cell fate specification and the epigenetic states that precede it. I will develop a novel strategy to simultaneously profile many factors involved in gene regulation in the same cell. Its successful implementation will give insight into transcriptional control at unprecedented modality, revealing the causal relationships between histone modifications, spatial positioning within the nucleus, Polycomb group proteins, and others. Next, I will pursue several molecular memory strategies to obtain recordings of past regulatory states, followed by multi-omic readouts at later developmental times. Such retrospective analyses enable linking fate decisions to past molecular events in the same cell, thereby permitting careful reconstruction of the molecular trajectories underlying cell fate choice. Finally, these and previously developed single-cell methods will be applied to unravel the gene-regulatory mechanisms that govern lineage determination in early mouse development. ver más
30/09/2026
2M€
Duración del proyecto: 67 meses Fecha Inicio: 2021-02-17
Fecha Fin: 2026-09-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-02-17
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCH... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5