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PAINTing the architecture of the totipotency gene network during early mammalian development

Project description

Genomic architecture in the embryo

Chromatin organisation is central for correct transcriptional activity and other key aspects of cell biology. However, the genomic architecture of totipotent cells in the early embryo remains uncharacterised. The aim of the EU-funded EmbryoPAINT project is to understand if precise genomic rearrangements drive cell fate decisions or if this is a stochastic process. Using 3D super-resolution microscopy and DNA paints, researchers will study the physical structure and architecture of totipotency and pluripotency genes in single stem cells in the whole embryo. Project results will provide important insight into the process of mammalian development.

Objective

The three-dimensional architecture of the genome regulates its fundamental functions such as the transcription or replication of DNA. Thus, chromatin organisation is crucially important for key aspects of cell biology, such as the differentiation of stem cells in the early embryo. While recent studies have shown that the mammalian genome rearranges extensively towards a more ordered state after the first few embryonal divisions, many fundamental questions remain unanswered. For example, it is not known whether totipotent cells have a well-defined genomic architecture or whether this architecture is highly heterogeneous between different cells and embryos. Further, it is unclear if early cell fate decisions are driven by a reproducible coordinated rearrangement of pluripotency-related genes, or if this is stochastic process. These questions could best be tackled by directly assessing the physical genome structure and architecture of pluripotency genes in single stem cells inside the whole embryo. In my project, I will pursue this ambitious aim by exploiting recent breakthroughs in 3D super-resolution microscopy, namely the development of an inverted lattice light-sheet microscope, highly multiplexed oligo-DNA-PAINT, and advanced computational algorithms, to study the physical 3D architecture of the genomic network of totipotency and pluripotency genes. Thus, I will for the first time be able to unravel the structural determinants of the transition from totipotency to the pluripotent and differentiated state during early mammalian development.

Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution
€ 162 806,40
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost
€ 162 806,40