Characterization of a Sox2 pathway in postembryonic schistosome parasites

胚胎后血吸虫寄生虫中 Sox2 途径的表征

• 批准号: 8622469
• 负责人: Emmitt Randolph Jolly
• 金额: $ 7.93万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8622469
• 关键词: Address; Adult; Affect; Antibodies; Biological Assay; Biology; Boxing; Caenorhabditis elegans; Cell Culture Techniques; Cells; Cessation of life; Chronic; Development; Developmental Gene; Digestion; Disease; Dominant-Negative Mutation; Down-Regulation; Drosophila genus; Drug Targeting; Embryo; Embryonic Development; Erinaceidae; Erythrocytes; Fertilization; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Genome; Goals; Helminths; Homologous Gene; Human; Immunohistochemistry; Infection; Invaded; Knowledge; Malignant Neoplasms; Mammals; Measures; Methods; Molecular; Molecular Target; Morphology; Mus; Muscle Development; Neuronal Differentiation; Neurons; Normal Range; Organism; Parasites; Pathway interactions; Pattern; Pharmaceutical Preparations; Praziquantel; Primordial Gut; Process; Proteins; Proteomics; RNA Interference; Regulation; Role; Schistosoma; Schistosome Parasite; Schistosomiasis; Sonic Hedgehog Pathway; Sporocysts; Staging; Stem cells; Testing; Time; Transcript; Transcription Coactivator; Whole Organism; asexual; blastocyst; design; drug development; egg; neuron development; novel; overexpression; pluripotency; public health relevance; response; sex; success; transcription factor

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.

项目摘要 血吸虫感染了全世界超过2.07亿人。每年有超过25万人死于 相关并发症。血吸虫病的治疗主要依靠药物， 吡喹酮，已经使用了30多年。尽管我们对寄生虫的了解 自从近年来基因组测序以来， 在分子水平上的发展一直在增加，使得合理设计的药物的鉴定 目标很难。因此，重要的是开始定义的基本途径，重要的是， 生存能力。我们希望通过定义血吸虫所需的早期遗传途径来实现这一目标 在感染人类宿主后立即发育。本研究将聚焦性别决定区Y盒 2（Sox 2）蛋白。Sox 2是一种转录激活因子，在囊胚形成前表达， 哺乳动物的发育和胚胎发育所必需的。Sox 2表达与 多能性和干细胞、神经元分化、肠道发育和癌症。虽然大多数哺乳动物 Sox 2的研究已经在细胞培养中进行了分析，Sox 2基因在感染后表达。 哺乳动物宿主在囊胚形成后很久。我们将确定不适当的时间的影响 Sox2基因在潜在的Sox2靶点和溶酶体活力上的表达和下调， 特别强调的是肠道的发育。我们假设Sox2是必需的， 正常的肠道发育。这项研究提供了一个新的机会，以了解影响， Sox2在生物体水平上。