Background for CRESCO
High frequency of pregnancy loss
Some of the most profound events in the life of an organism, with far-reaching consequences for development and health, happen during the very early stages of existence. These include completion of meiosis, merging of parental genomes at fertilization, and reprogramming of chromatin during early embryo development. Despite its evolutionary conservation, conception is associated with chromosome errors and an unexpectedly high frequency of pregnancy loss and congenital disorders.
In CRESCO, we propose to use cutting-edge technology to study in exquisite detail the roles of dynamic and reversible epigenetic and epitranscriptomic modifications in oocyte and the early embryo, including their functions in genome stability, chromosome segregation and retrotransposon activity. An overarching goal is to understand the role of epigenetic and epitranscriptomic information in the passing of life from one generation to the next in the One Health perspective.
Investigating human and lifestock embryos
We will design gene-targeted models and use single-cell and single-nucleotide resolution analysis to gain precise information on novel and known epigenetic and epitranscriptomic modifications required for maintaining chromosomal homeostasis during reprogramming of the oocyte and the early embryo.
Candidate factors identified will be pursued to understand their roles in healthy human and livestock embryo development. Livestock will add a crucial dimension, especially as the breeding focus for several decades has resulted in Norwegian cattle and swine being world-leaders in reproductive efficacy.
We envision technological breakthroughs: stepping beyond genetic selection of human preimplantation embryos and animals, we set to discover pathways that effect germline and embryonic defects to improve human and livestock health.
Primary objective of CRESCO
- Reveal mechanisms of fertilization by understanding reprogramming of the oocyte genome during growth, meiotic progression, fertilization, and embryo development - and its significance for genome stability and healthy development across species.
Secondary objectives of CRESCO
- Develop state-of-the-art epigenetic and epitranscriptomic single-cell and single-nucleotide resolution assays.
- Identify novel epigenetic and epitranscriptomic signatures associated with successful fertilization and healthy development in mice, livestock animals – and ultimately in humans.
- Characterize the biochemical activities of novel writers, readers and erasers of such signatures.
- Assess the function of these epigenetic and epitranscriptomic modifiers and their implications for healthy embryo development and future health.
- Develop novel technologies to assess the quality of the fertilized egg and to improve the outcome of in vitro fertilization treatment.