MACROMOLECULAR TRANSPORT IN ASEXUAL MALARIA PARASITES

这项建议的长远目标是使运输 疟原虫感染的红细胞中的途径。在红细胞内 在周期中，寄生虫积极重塑宿主细胞的胞质溶胶和血浆 膜，以满足他们的代谢要求，并确保他们的长期 长期生存。维持复杂宿主的途径和过程 细胞-寄生虫的关系在生物化学方面知之甚少， 水平有证据表明，血液阶段的寄生虫内化膜 从外部介质通过一个途径， 绕过红细胞胞质溶胶。确定和 这种新途径的特征刺激了研究人员， 探索疟疾研究的新领域，包括寄生虫转染， 反义RNA和使用不透膜药物的化疗。 基本转运途径的表征将提供 有机会设计策略来破坏（或利用）这些过程 来降低寄生虫的生存能力核糖体失活蛋白质 植物将被用来研究大分子的运输途径， 评估它们的抗疟疾功效。这些蛋白质被选中 因为它们具有良好生物化学特性， 体外抗病毒和抗肿瘤细胞毒性。细胞毒性似乎 在生物体/细胞快速复制的情况下是最好的 就像疟原虫和其他传染病一样。的 核糖毒素的寄生虫内靶点和细胞毒性的基础将是 研究了对寄生虫蛋白质和核酸合成的影响 将研究DNA稳定性和复制。取决于它们的 作用模式，结合其他已知的复制方案， 病原体，这些研究的结果可能揭示了机会 其中核糖毒素可用于治疗疟疾和其它疾病， 传染病

The long term objective of this proposal is to characterize transport pathways in Plasmodium-infected erythrocytes. During the erythrocytic cycle, parasites actively remodel the host cell cytosol and plasma membrane to meet their metabolic requirements and to insure their long term survival. The pathways and processes that maintain the complex host cell-parasite relationship are poorly understood at the biochemical level. There is evidence that blood-stage parasites internalize membrane impermeable molecules from the external medium through a pathway that bypasses the erythrocyte cytosol. The identification and characterization of this new pathway has stimulated investigators to pursue new areas in malaria research, including parasite transfection, antisense RNA and Chemotherapy using membrane-impermeable drugs. Characterization of essential transport pathways will provide the opportunity to design strategies to disrupt (or utilize) these processes to compromise parasite viability. Ribosome inactivating proteins from plants will be used to investigate macromolecular transport pathways and evaluated for their antimalarial efficacy. These proteins were selected since they are biochemically well characterized and produce specific antiviral and antitumor cytotoxicity in vitro. Cytotoxicity appears to be best in situations where the organisms/cells are rapidly replicating as would be the case for Plasmodium and other infectious diseases. The intraparasitic targets of ribotoxins and basis of cytotoxicity will be investigated. Effects on parasite protein and nucleic acid syntheses and DNA stability and replication will be investigated. Depending on their mode of action, combined with the known replication schemes of other pathogens, the results from these studies may reveal opportunities whereby ribotoxins may be applied for the treatment of malaria and other infectious diseases.