Nuclear-cytoplasmic interactions in mammalian embryos

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The long-term objective of my research program is to investigate the biological mechanisms that orchestrate the genetic and epigenetic programs supporting early development in mammals. Cattle embryos reconstructed by nuclear transfer, i.e. animal cloning, are used to analyze the molecular and cellular interactions between donor cell nuclei and oocyte host cytoplasm during development. Particular interest is focused on the phenomenon of chromatin remodeling by the host ooplasm, which engenders substantial reprogramming to the transcriptional activity of the donor cells. The working hypothesis is that the abnormal epigenetic reprogramming of the chromatin, particularly in imprinted genes necessary for early development, is the main cause of embryonic death. The implications of this research are widespread. First, epigenetics remains a widely unknown field of biology and a better understanding of the mechanisms controlling the remodeling of chromatin in reconstructed embryos will be useful to many areas of life science. Second, the plasticity of embryos has already drastically changed the animal industry by enabling a faster propagation of genetically superior animals. In the future, these new technologies will enable the rescuing and protection of precious animal resources that are currently being threatened. Finally, improvements in nuclear transfer methodology will offer a much more efficient means of improving the genotype of animals for the benefit of Canadians.