TROPICAL DISEASE RESEARCH UNIT

本次热带疾病续展申请的总体目标 研究单位将检查对以下事件至关重要的特定分子事件 丝虫和曼氏血吸虫的发育及功能 将这些知识和相关技术应用到防爆设计中 蠕虫疫苗。当前的应用是一个多学科的应用 整合科学方法NAD的协作计划 免疫学、分子生物学、生物化学、细胞学的技术工具 生物学和寄生虫学应用于研究淋巴的特定方面 丝虫病和曼氏血吸虫病。四个方面的具体目标 包括的项目包括： 项目1。确定重组丝虫病抗原的特定表位 可诱导对马来丝虫感染的保护性免疫。 2.阐明保护机体的免疫机制 丝虫抗原可诱导抗药性。 项目21.定义马来分枝杆菌和蛔虫中的基因，这些基因给出 上升为反式剪接的转录本。 2.定义引导启动和启动的序列元件 从其剪接的短的非多腺体RNA的终止 先导外显子被推导出来。 项目3 1.定义生化结构并克隆68K 保护性曼氏血吸虫抗原。 2.阐明68K疫苗诱导的免疫学基础 并提出了提高其药效的检测方法。 项目4 1.表征曼氏葡萄球菌的生化性质 尾丝虫糖唇。 2.研究了不同温度下糖萼的释放机制。 尾蚴向血吸虫的转化。 这些项目是基于对实验动物和血清的研究 人类志愿者和利用体外操作的致病因素 有机体。每一项目标的实现都依赖于科学和 项目1-2、项目1-3、项目2-3、 项目3-4和核心设施提供蠕虫、淋巴细胞 克隆技术和超微结构分析。

The overall objective of this renewal application for a Tropical Disease Research Unit is to examine specific molecular events critical to development and function of filarial parasites and Schistosoma mansoni and apply this knowledge and associated technologies to the design of anti- helminthic vaccines. The current application is a mutlidisciplinary collaborative program that integrates the scientific approaches nad technical tools of immunology, molecular biology, biochemistry, cell biology, and parasitology applied to study specific aspects of lymphatic filariasis and schistosomiasis mansoni. The specific aims of the four projects included are to: Project 1 . Define specific epitopes of a recombinant filarial antigen which induce protective immunity against B. malayi infection. 2. Elucidate the immune mechanisms by which protective filarial antigens induce resistance. Project 2 1. Define the genes in B. malayi and Ascaris which give rise to transcripts which are trans-spliced. 2. Define the sequence elements which direct initiation and termination of the short non-polyadenylated RNA from which the spliced leader exon is derived. Project 3 1. Define the biochemical structure and clone a 68K protective S. mansoni antigen. 2. Elucidate the immunologic basis of 68K vaccine-induced resistance and determine methods to enhance its efficacy. Project 4 1. Characterize the biochemical nature of the S. mansoni cercarial glycocalyx. 2. Study the mechanisms of glycocalyx release during transformation of cercariae to schistosomula. These projects are based on studies in experimental animals and sera from human volunteers and utilize in vitro manipulation of the causative organisms. Achievement of the goals of each is dependent on scientific and technical interactions between Projects 1-2, Projects 1-3, Projects 2-3, and Projects 3-4 and core facilities providing helminths, lymphocytes cloning expertise, and ultrastructure analyses.