TRANSFECTION OF MALARIA

疟疾是一种原生动物寄生虫，可引起世界范围内的发病率和 死亡率。对这种致命的人类病原体的治疗和预防 由于毒品的出现和迅速传播而变得非常复杂 抵抗。对疟疾耐药表型的研究揭示 肿瘤细胞多药耐药(MDR)的惊人相似性 台词。在这两种情况下，药物都被主动地从耐药细胞中泵出 这种外流可以被钙通道阻滞剂逆转。在肿瘤学 将多药耐药基因导入敏感细胞导致 耐药性的发展和证明MDR之间的关键关系 基因和抗药性。一种新开发的转基因系统有望 首次允许直接确定和研究 多药耐药基因在疟疾耐药分子发病机制中的作用 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制和生物学。深入研究 将对用于研究疟疾的分子技术进行培训 通过精炼和扩展新近开发的 疟疾转染系统。项目第二阶段将利用 技术和改进的转导系统在第一阶段开发进行测试 疟疾多药耐药基因。如果这些基因确实介导了耐药性的相互作用 多药耐药基因编码的P-糖蛋白同源物和 将执行逆转代理。 因此，该项目的长期目标是：1)提供 分子生物学和生物科学领域的强化教学和研究背景 疟疾的发病机制和2)提供了良好的基础独立 利用沙门氏菌进行耐药分子基础的实验室研究 基因导入系统。

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.