Project description
Metabolic and epigenetic regulation in early development
During embryonic development, a series of complex events take place, including cellular differentiation, tissue formation, and the establishment of organ systems, all governed by intricate genetic and epigenetic regulation. These changes are influenced by various internal and external factors, such as metabolic shifts, signalling pathways, and environmental cues. The ERC-funded ChroMeta project aims to elucidate the relationship between metabolic changes and specific epigenetic outcomes during embryonic development. Previous data suggest that metabolic rewiring during embryo implantation impacts chromatin dynamics. The research team will employ multi-omics approaches to test various hypotheses and delineate the underlying mechanisms. Project findings will fuel further research into the molecular processes involved in early pregnancy.
Objective
When environment of the embryo changes or when development progresses metabolic reactions are rapidly affected. These alterations to chemical reactions are coupled to epigenetic memory. However, without mechanistic data on how this coupling occurs it is difficult to understand how normal embryogenesis can proceed. This project will elucidate how metabolic changes result in specific epigenetic outcomes and address the function of such regulation. As a model we will use mouse implantation, a process tightly linked to dramatic alterations to chromatin and transcription. We found that this is also associated with extensive metabolic rewiring and that disrupting metabolic flows results in both lineage-specific and mark-specific changes to chromatin. While multiple studies uncovered that metabolism fuels chromatin modifiers with co-factors, the fundamental biological question of how specificity is achieved remains unanswered. Here we will address this challenge by directly testing the three most likely hypotheses: 1) that metabolic reactions shuttle into the nucleus where they specifically fuel chromatin changes; 2) that chromatin-bound metabolic enzymes regulate gene expression and 3) that only specific chromatin modifiers are sensitive to metabolic changes. To address these questions, we will go beyond description as we supplement multi-omic approaches with mechanistic experiments both in vitro and in vivo. Firstly, will use perturbations of nuclear metabolic enzymes and their chromatin binding. Secondly, we will implement protein engineering to render chromatin modifiers resistant to the availability of their co-factors. By uncoupling epi-metabolic regulation, we seek not only to uncover its importance for controlling chromatin states but also the implantation developmental program. This project will form a framework of how future studies can mechanistically unravel intertwined regulatory processes and assess the role of environment and nutrition in early pregnancy.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesclinical medicineobstetrics
- medical and health scienceshealth sciencesnutrition
- medical and health sciencesclinical medicineembryology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
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Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1165 Kobenhavn
Denmark