TRANSFECTION OF MALARIA

疟疾是一种原生动物寄生虫，在世界范围内引起发病率， mortality. 治疗和预防这种致命的人类病原体， 由于毒品的出现和迅速蔓延， 阻力 对疟疾抗药性表型的研究表明， 肿瘤细胞中多药耐药（mdr）惊人相似性 线 在这两种情况下，药物都被积极地泵出耐药细胞 这种流出被钙通道阻滞剂逆转。 肿瘤性 细胞MDR基因转染到敏感细胞中导致 耐药性的发展，并证明了耐多药之间的关键关系， 基因和抵抗力 一种新开发的转染系统有望 第一次允许直接确定和研究 疟疾MDR基因耐药的分子发病机制。 PSA奖的第一阶段将涉及分子的教学研究， 疟疾寄生虫的发病机理和生物学。 密集调研 在疟疾研究中使用的分子技术的培训将 通过完善和扩大最近开发的 疟疾转染系统。 项目第二阶段将利用 在第一阶段开发的技术和改良的转染系统， 疟疾mdr基因 如果这些基因确实介导了抗药性相互作用 mdr基因编码的P-糖蛋白同源物与 将使用逆转剂。 因此，该项目的长期目标是：1）提供 密集的教学和研究背景的分子生物学和 疟疾的发病机制和2）提供了一个良好的基础， 耐药性的分子基础的实验室研究， 基因转染系统

Malaria is a protozoan parasite which causes worldwide morbidity and mortality. Treatment and prophylaxis of this deadly human pathogen has been greatly complicated by the emergence and rapid spread of drug resistance. Studies of the phenotype of drug resistance in malaria reveal striking similarities to multiple drug resistance (mdr) in neoplastic cell lines. In both instances drugs are actively pumped out of resistant cells and this efflux is reversed by calcium channel blockers. In neoplastic cells the transfection of mdr genes into sensitive cells leads to the development of resistance and proves the crucial relationship between mdr genes and resistance. A newly developed transfection system promises to allow for the first time the direct determination and study of the role of malaria mdr genes in the molecular pathogenesis of drug resistance. Phase 1 of the PSA award will involve the didactic study of the molecular pathogenesis and biology of the malaria parasite. Intensive research training in the molecular techniques utilized in studying malaria will be provided through the refining and expansion of the recently developed malaria transfection system. Phase 2 of the project will utilize the skills and modified transfection system developed in Phase 1 to test malaria mdr genes. If these genes do mediate drug resistance interactions between the P-glycoprotein homologue which the mdr genes encode and reversal agents will be performed. The long-term goals of the project therefore are to: 1) provide an intensive didactic and research background in the molecular biology and pathogenesis of malaria and 2) provide a sound basis for independent laboratory studies of the molecular basis of drug resistance utilizing a gene transfection system.