Characterisation of a signal transduction pathway in the early embryo

在实验室中创造胚胎对辅助生殖技术（ART）和使用胚胎干细胞的潜在细胞治疗都很重要。然而，早期胚胎的发育尚不清楚。在实验室里制造胚胎是昂贵的，其中很大一部分成本与技术的相对低效率有关，因为由此产生的胚胎死亡率很高。通常情况下，45 - 80%的ART产生的胚胎不能存活第一周。激素是调节身体正常功能的基本化学信使。早期胚胎发育依赖于胚胎细胞自身产生的特殊激素的作用。这些激素的作用是它们正常生存所必需的。抗逆转录病毒治疗会损害其中几种激素的产生和作用。目前，关于这些胚胎激素如何作用于胚胎以促进其存活，还没有详细的描述。细胞通过改变一些充当开关的细胞内蛋白质的活性来响应外部激素。“开关”设置的组合模式被激素修改，而激素反过来又可以改变基因表达的模式。这个项目将扩展我们对被称为PAF的胚胎激素作用性质的广泛研究。这种激素作用于胚胎基因表达模式的信号变化的机制将被研究。了解这些胚胎激素是如何起作用的，将在未来显著提高胚胎的生存能力。

The creation of embryos in the lab is important in assisted reproductive technology (ART) and potentially in cell therapies using embryonic stem cells. Yet, the development of the early embryo is not well understood. Creation of embryos in the lab is expensive and much of this cost is related to the relative inefficiency of the technology due to the high mortality of the resulting embryos. Typically, 45 - 80% of embryos produced by ART do not survive the first week. Hormones are essential chemical messengers that regulate the normal functions of the body. Early embryo development is dependent on the action of special hormones that are produced by the embryonic cells themselves. The actions of these hormones are necessary for their normal survival. ART compromises the production and action of several of these hormones. Currently, there is not a detailed picture of how these embryonic hormones act on the embryo to promote their survival. Cells respond to outside hormones by changing the activity of a number intracellular proteins that act as on-off switches. The combinatorial pattern of 'switch' settings is modified by hormones, which in turn can act to change the pattern of gene expression. This project will extend our extensive studies on the nature of action of the well-described embryonic hormone known as PAF. The mechanism by which this hormone acts to signal changes in the pattern of the embryo's gene expression will be investigated. An understanding of how these embryonic hormones work will in the future allow for significant improvements in embryo viability.