Characterization of a Sox2 pathway in postembryonic schistosome parasites

项目摘要 全世界有超过2.07亿人感染血吸虫病。每年有超过25万人死于 血吸虫相关并发症。血吸虫病的治疗主要依靠药物， 已经使用了30多年的吡喹酮。尽管我们对血吸虫寄生虫的了解 自从最近几年基因组测序以来，我们对血吸虫的理解 分子水平的发展一直是渐进的，使得对合理设计的药物的识别 目标很难确定。因此，开始确定对血吸虫重要的基本途径是很重要的 生存能力。我们希望通过确定血吸虫所需的早期遗传途径来朝着这一目标前进 在感染人类宿主后立即发展。这项研究将聚焦于性别决定区域Y-box 2(Sox2)蛋白存在于血吸虫体内。Sox2是一种转录激活子，在胚泡形成前表达。 哺乳动物的发育，是胚胎发育所必需的。SOX2表达式与 多能性和干细胞、神经元分化、肠道发育和癌症。尽管大多数哺乳动物 Sox2的研究已经在细胞培养中进行了分析，血吸虫感染A细胞后表达该基因。 哺乳动物在囊胚形成后很久才有的宿主。我们将确定不适当的时间影响 Sox2基因在潜在的Sox2靶点上的表达和下调对血吸虫存活率的影响 特别强调血吸虫肠道的发育。我们假设Sox2是 血吸虫肠道发育正常。这项研究提供了一个新的机会来理解 SOX2在生物体水平上。

Project Summary Schistosomiasis infects more than 207 million people worldwide. More than 250,000 people die annually from schistosome-associated complications. Treatment for schistosomiasis relies primarily on the drug, praziquantel, which has been in use for more than 30 years. Although our knowledge of schistosome parasites has expanded since the genome was sequenced in recent years, our understanding of schistosome development at the molecular level has been incremental, making the identification of rationally designed drug targets difficult. Therefore, it is important to begin to define the basic pathways important for schistosome viability. We hope to progress toward this goal by defining early genetic pathways necessary for schistosome development immediately after infecting a human host. This study will focus the Sex determining region Y-box 2 (Sox2) protein in schistosomes. Sox2 is a transcriptional activator that is expressed prior to blastulation in mammalian development and is necessary for embryogenesis. Sox2 expression is associated with pluripotency and stem cells, neuronal differentiation, gut development, and cancer. Although most mammalian studies on Sox2 have been analyzed in cell culture, schistosomes express this gene after infecting a mammalian host long after formation of a blastula. We will determine the effect of inappropriate temporal expression and down regulation of the Sox2 gene on potential Sox2 targets and on schistosome viability, with a particular emphasis on the development of the schistosome gut. We hypothesize that Sox2 is required for normal gut development in schistosomes. This study provides a novel opportunity to understand the effect of Sox2 at the organism level.