Nuclear-cytoplasmic interactions in mammalian embryos

我的研究计划的长期目标是研究协调支持哺乳动物早期发育的遗传和表观遗传程序的生物学机制。通过核移植(即动物克隆)构建的牛胚胎用于分析胚胎发育过程中供体细胞核与卵母细胞胞质之间的分子和细胞相互作用。特别关注的是宿主卵浆染色质重塑的现象，这会对供体细胞的转录活性产生实质性的重编程。工作假设是，染色质的异常表观遗传重编程，特别是在早期发育所必需的印记基因中，是胚胎死亡的主要原因。这项研究的影响是广泛的。首先，表观遗传学仍然是生物学中一个广泛未知的领域，更好地理解控制重构胚胎染色质重塑的机制将对生命科学的许多领域有用。其次，胚胎的可塑性已经极大地改变了畜牧业，使具有遗传优势的动物能够更快地繁殖。未来，这些新技术将使拯救和保护目前受到威胁的宝贵动物资源成为可能。最后，核移植方法的改进将提供一种更有效的手段来改进动物的基因，造福于加拿大人。

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.