EMBRYOGENESIS AND LARVAL MORPHOGENESIS IN TWO FILARIAE

两种丝虫的胚胎发生和幼虫形态发生

• 批准号: 2837429
• 负责人: JULIET A FUHRMAN
• 金额: $ 19.13万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2837429
• 关键词: DNA binding protein; DNA footprinting; Filarioidae; SDS polyacrylamide gel electrophoresis; X ray crystallography; chitin; crosslink; developmental genetics; enzyme activity; filariasis; gel mobility shift assay; gene expression; host organism interaction; intracellular parasitism; life cycle; microorganism genetics; microorganism reproduction; molecular cloning; polymerase chain reaction; polysaccharides; protein sequence; virulence

Filarial parasites cause a wide variety human and animal diseases, including human elephantiasis and river blindness, and dog heartworm. All filarial species require an anthropod vector for transmission to new hosts. The parasite stage that infects the vector is the first larval stage, or microfilaria, which must persist in the blood or tissues of the vertebrate host for successful transmission. This application proposes to study processes in filarial embryogenesis leading to the production of microfilariae that can successfully effect transmission. The development of the first stage larva in utero follows either of two patterns in all filariae: one pattern produces sheathed microfilariae, and the other produces microfilariae that hatch free of the eggshell and are nonsheathed. Examples of each pattern will be studied to understand common and distinct patterns of gene expression. The metabolism of a complex polysaccharide, chitin, will be analyzed, to understand the regulation of its synthesis, modification, and degradation during microfilarial morphogenesis. In particular, the relationship of chitin metabolism with eggshell growth, sheath restructuring, and hatching will be studied by biochemical and molecular analyses. The use of protein crosslinking to produce protective structures such as the eggshell, sheath and cuticle will be studied as it relates to embryonic growth and shape change for the two different patterns of development. Specific substrates for crosslinking reactions will be compared between sheathed and nonsheathed microfilarie as they develop in utero. Finally, the patterns of gene expression will be compared by RNA differential display between early and late stages of embryos in two different species, in order to identify new therapeutic targets. The ability to disrupt filarial embryogenesis would be significant for controlling transmission of all filarial infections, and for controlling disease in Onchocercal infections. The biochemical basis of embryonic growth and morphogenesis will be analyzed by these studies in order to assess the potential for interrupting microfilarial production.

丝虫寄生虫引起多种人类和动物疾病， 包括人类象皮病和河盲症以及狗心丝虫病。 所有丝虫物种都需要节肢动物载体才能传播到新的物种 主机。 感染媒介的寄生虫阶段是第一个幼虫 阶段，或微丝蚴，必须持续存在于血液或组织中 成功传播的脊椎动物宿主。 这个应用程序 提议研究丝虫胚胎发生过程，从而导致 产生能够成功传播的微丝蚴。 第一阶段幼虫在子宫内的发育遵循以下两种方式之一 所有丝虫的模式：一种模式产生有鞘的微丝蚴， 另一个产生脱离蛋壳孵化的微丝蚴 是无护套的。 将研究每种模式的示例以理解 基因表达的常见和独特模式。 一个人的新陈代谢 将分析复杂的多糖、几丁质，以了解 其合成、修饰和降解过程的调控 微丝虫形态发生。 特别是甲壳素的关系 蛋壳生长、鞘重组和孵化过程中的新陈代谢 通过生化和分子分析进行研究。蛋白质的利用 交联以产生保护结构，例如蛋壳， 将研究鞘和角质层，因为它与胚胎生长和 形态变化适合两种不同的发展模式。 具体的 将比较带护套的交联反应底物 和无鞘微丝蚴在子宫内发育。 最后， 通过RNA差异显示来比较基因表达模式 在两个不同物种的胚胎早期和晚期之间 以便确定新的治疗靶点。 颠覆能力 丝虫胚胎发生对于控制传播具有重要意义 所有丝虫感染，以及控制盘尾丝虫疾病 感染。 胚胎生长和形态发生的生化基础 将通过这些研究进行分析，以评估 中断微丝蚴的产生。