VARIANT SURFACE GLYCOPROTEINS OF TRYPANOSOMA CRUZI

克氏锥虫表面糖蛋白变异体

• 批准号: 2057093
• 负责人: SIMON PAUL
• 金额: $ 8.81万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057093
• 关键词: DNA; Escherichia coli; Trypanosoma cruzi; binding proteins; complementary DNA; disease vectors; enzyme substrate; exo alpha sialidase; gene expression; genetic mapping; genetic transcription; glycoproteins; glycosidases; glycosylation; glycosyltransferase; host organism interaction; membrane proteins; molecular cloning; molecular genetics; nucleic acid sequence; phosphatidylinositols; phospholipase C; protein structure function; proteoglycan; sialyltransferases; transfection /expression vector; tropical medicine; trypanosomiasis

The purpose of this proposal is to enable the principal investigator to develop research skills in fundamental science, in the specific area of infectious disease and molecular parasitology, to facilitate his development into an independent investigator capable of initiating and sustaining a research program. The proposal consists of two phases. The first phase is a research training phase, including didactic elements and laboratory research, which progresses to a more research-intensive and independent second phase. The principal investigator has identified the field of parasitology and tropical medicine as one in which he wishes to pursue a research career. The specific area of the research proposal, in both phases, concerns Trypanosoma cruzi, the causative agent of Chagas' disease, a chronic illness affecting over 20 million people in Mexico, Central and South America. This obligate intracellular parasite has a complex life cycle, with multiple developmental stages in the insect vector and the mammalian host. The immune system of the host mounts a strong response to the organisms but sterile immunity is rarely if ever achieved, as the parasite lies protected in the cytoplasm of host cells during its replicative phase. Gene cloning has recently revealed that several surface glycoproteins from the infective stages of Trypanosoma cruzi, which were identified by disparate means and were thought to be functionally distinct, are actually members of a large family. The variation among these sequences (as yet unpublished) is large: indeed, the relationship between some sequences that are now presumed to be members of the family night not have been noted if they did not all contain two copies of an amino acid motif that was previously identified as being unique to a group of bacterial neuraminidases (it is not shared by viral neuraminidases). More extensive searches of protein databases suggest that this motif is very rare and very significant, and that it may also be found in several proteins whose functions involve sugar recognition. Individual cells appear to simultaneously express multiple members of this gene family, which may be the key to the virulence and pathogenicity of Trypanosoma cruzi. The purposes of the proposed research are to define the enzymatic and glycan-binding activities of individual members of the gp85 family, to study the regulation of gp85 gene expression (both in individual infective cells, in clones, and during the life cycle), and to determine whether these activities are important in host cell penetration by Trypanosoma cruzi.

该提案的目的是使主要研究人员能够 在基础科学方面发展研究技能，在特定领域 传染病和分子寄生虫学，以促进他 发展成为能够启动和的独立调查员 维持研究计划。 该提案包括两个阶段。 这 第一阶段是研究培训阶段，包括教学元素和 实验室研究，发展到更加研究和 独立的第二阶段。 首席调查员已经确定了 他希望的寄生虫学和热带医学领域 从事研究职业。 研究建议的特定领域， 这两个阶段都涉及Crypanosoma Cruzi，这是Chagas的致病药物 疾病，一种慢性疾病，影响墨西哥超过2000万人 中美洲和南美。 这种强制性细胞内寄生虫有一个 复杂的生命周期，昆虫载体有多个发育阶段 和哺乳动物主人。 宿主的免疫系统安装强大 对生物体的反应，但无菌免疫力很少实现， 由于寄生虫在宿主细胞的细胞质中受到保护。 复制阶段。 基因克隆最近揭示了来自 克鲁齐锥虫的感染阶段，由 不同的手段，被认为在功能上是不同的，实际上是 一个大家庭的成员。 这些序列之间的变化（到目前为止 未发表）很大：的确，某些序列之间的关系 现在假定是家庭之夜的成员 他们并不全部包含两个氨基酸基序的副本 以前被认为是一组细菌独有的 神经氨酸酶（病毒神经氨酸酶不会共享）。 更广泛 对蛋白质数据库的搜索表明，此基序非常罕见，非常非常 重要的，并且也可以在几种蛋白质中找到 功能涉及糖识别。 单个细胞似乎 同时表达该基因家族的多个成员，这可能是 克鲁齐锥虫的毒力和致病性的关键。 这 拟议研究的目的是定义酶法和 GP85家族各个成员的聚糖结合活动， 研究GP85基因表达的调节（均在个体感染力中 细胞，克隆和在生命周期中），并确定是否 这些活性在锥虫瘤的宿主细胞渗透中很重要 克鲁兹。