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Elucidating the role of nuclear metabolism in embryo implantation

Project description

Nuclear metabolism and epigenetic regulation during implantation

Epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal structure without altering DNA sequences. During embryonic development, epigenetic changes play a pivotal role in determining lineage specification. With the support of the Marie Skłodowska-Curie Actions programme, the NucMeta project will focus on the role of metabolism on the epigenetic landscape during early development. Researchers will employ embryonic stem cell-derived trophoblast stem cells and investigate the regulatory role of specific metabolic enzymes in the nucleus. Using transcriptomic, genomic, and epigenomic data, they aim to uncover how nuclear metabolic activity directs gene regulation during embryo implantation.

Objective

Embryogenesis involves dynamic epigenetic and transcriptional changes as the zygote divides and cells differentiate into embryonic (epiblast) and extra-embryonic (primitive endoderm and trophectoderm) lineages. Metabolites serve as cofactors or substrates for chromatin-modifying proteins, thus shaping the global epigenetic landscape. Intriguingly, during early development, multiple metabolic enzymes translocate to the nucleus where they might fuel chromatin modifiers. How the interplay between nuclear metabolism and epigenetics regulates cell fate transitions remains unclear. With this proposal, I aim to unveil the role of nuclear metabolism in regulating lineage-specific phenotypes during early development, using implantation as a model. I will focus on this developmental stage as it is characterised by dynamic metabolic and chromatin rewiring. Since implantation relies on proper trophectoderm specification and maturation, I will use embryonic stem cell-derived trophoblast stem cells that transit between pre- and post-implantation-like states in vitro. Specifically, I will establish novel tools to target the degradation of key metabolic enzymes exclusively in the nucleus and assess the impact on gene expression and chromatin modifications. Moreover, I propose to identify the genomic targets and protein partners of nuclear metabolic enzymes. Ultimately, the integration of transcriptomic, genomic, and epigenomic data will unveil the metabolic determinants underlying gene expression and epigenetic changes at implantation.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 263 393,28
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

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