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DarkCellFader

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Uncovering the role and regulation of 3D DNA-RNA nuclear dynamics in controlling...

Uncovering the role and regulation of 3D DNA-RNA nuclear dynamics in controlling cell fate decisions At the onset of mammalian life, the first lineage specification decision is made where embryonic cells opt to become either part of the placenta or the future body. Proper regulation of this choice is crucial for subsequent develo... see more

31/05/2028

IMBA

2M€

Project Budget: 2M€

Project leader

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

Financing granted El organismo HORIZON EUROPE notifico la concesión del proyecto The day 2023-04-07

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

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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1 Participantes

IMBA

1.50M€ | Leader

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Project duration: 61 months Date Start: 2023-04-07
End date: 2028-05-31

Project leader

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 2M€

participation deadline Sin fecha límite de participación.

Project description At the onset of mammalian life, the first lineage specification decision is made where embryonic cells opt to become either part of the placenta or the future body. Proper regulation of this choice is crucial for subsequent development. However, we don’t know how the transcription program and 3D genome architecture arise, interconnect, and are controlled to determine the fate of each cell in a developing embryo. Recent studies, including my work, suggest that in addition to canonical mRNA-coding genes, RNAs from the dark parts of the genome (e.g., transposons, repeats, long-non-coding RNAs) play a significant role during these events, yet how specific classes of RNA regulate gene expression and nuclear architecture post fertilization remains elusive. The main aim of my proposal is to understand the interrelationship between 3D genome organization and the transcriptome across early development and to identify novel factors that lead to the first cell-fate decision and concomitant decrease in cell potency. Recent technical advances, which I co-developed, enabled simultaneous measurement of 3D genome organization and the transcriptome, and facilitated large-scale functional screens in early mammalian embryos. Thus, I now propose to generate spatiotemporal maps of 3D DNA and RNA organization from early mouse embryos at single-cell resolution (Obj.1) to build a complete picture of the relationships between nuclear architecture and emerging cell-type specific transcriptome that drive early cell fate choices. I will combine these data with large-scale in vivo perturbations targeting protein coding genes (Obj.2) and dark genome RNAs (Obj.3) to identify key inducers/regulators of lineage specification and to determine molecular mechanisms governing cell-state transitions. The proposed research will help us to control, correct, and eventually employ early stages of embryonic development and their high cell potency in vitro in reproductive medicine and stem cell research.

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