EXTRACELLULAR DEVELOPMENT IN VITRO OF MALARIA PARASITES

疟疾寄生虫的体外细胞外发育

• 批准号: 2061353
• 负责人: WILLIAM TRAGER
• 金额: $ 22.63万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2061353
• 关键词: Plasmodium falciparum; communicable disease transmission; erythrocyte membrane; fluorescence microscopy; host organism interaction; human tissue; immunological substance; intracellular parasitism; laboratory mouse; malaria; membrane proteins; microorganism growth; monoclonal antibody; protein kinase

Our work of the past 3 years has given us a method that supports extracellular development of a complete asexual cycle of the erythrocytic stage of the major human malaria parasite Plasmodium falciparum (l). Just as the method for continuous in vitro propagation of this parasite in cell culture, reported from our laboratory in 1976 (26), made possible the extensive and brilliant work in molecular biology that has increased our understanding of the genetics of p falciparum and of the nature of chloroquine resistance, and has led to the identification of an array of candidate antigens that give promise for an effective erythrocytic stage vaccine (27), even so the further development of our axenic culture method will lead to deeper insights into the nature of the relationship between the parasite and its host erythrocyte. Our first aim therefore is to improve the axenic culture method. This will facilitate all further work. it would also provide for new approaches to vaccine development and studies of drug action. A second major aim will exploit the axenic development of merozoites into rings and early trophozoites to study the export from the parasites of specific proteins that in nature become associated with cisternae in the host erythrocyte or with the erythrocyte plasma membrane. Will these exported proteins form membranous structures in the acellular medium of axenic culture, where the rings are developing without a parasitophorous membrane? Comparative studies with ring-stage parasites that retain their parasitophorous membrane, prepared by lysis from host erythrocytes, may reveal a role for this membrane. Finally, the induction and development of gametocytes will be studied, with special reference to the greater formation of gametocytes in young erythrocytes. Results of the proposed work will contribute to understanding the physiology of the erythrocytic stages of malaria parasites and will bear on fundamental problems in intracellular parasitism.

我们过去三年的工作为我们提供了一种支持的方法 细胞的完整无性周期的细胞外发育 人类主要疟疾疟原虫恶性疟原虫（L）的阶段。 只是 作为这种寄生虫在细胞中连续繁殖的方法 1976年我们实验室报告的文化（26）使得 在分子生物学方面的广泛而出色的工作，这增加了我们的 理解p恶性的遗传学和对的本质 氯喹的耐药性，并导致了一系列阵列 候选抗原有望有效的红细胞阶段 疫苗（27），即使如此，我们的轴承培养方法的进一步发展 将导致更深入地深入了解之间关系的性质 寄生虫及其宿主红细胞。 因此，我们的第一个目标是 改善轴突培养方法。 这将有助于所有进一步的工作。 它还将提供疫苗开发的新方法， 药物作用研究。第二个主要目标将利用轴承 将梅罗寄生虫开发到环和早期滋养体中，以研究 从自然界中的特定蛋白质的寄生虫出口 与宿主的红细胞或红细胞相关 质膜。 这些出口的蛋白会形成膜结构 在轴承培养的细胞介质中，环正在发展 没有寄生膜？ 与环阶段的比较研究 保留其寄生膜的寄生虫，通过裂解制备 从宿主的红细胞中，可能揭示了该膜的作用。 最后， 将研究配子细胞的诱导和发展，并具有特殊 参考年轻的红细胞中配子细胞的更大形成。 拟议工作的结果将有助于理解 疟疾寄生虫的红细胞阶段的生理学，将承受 关于细胞内寄生虫的基本问题。