MACROMOLECULAR TRANSPORT IN ASEXUAL MALARIA PARASITES

这项提议的长期目标是描述交通运输的特点 感染疟原虫的红细胞中的通路。在红细胞增多症期间 循环，寄生虫主动重塑宿主细胞胞浆和胞浆 以满足他们的代谢需求，并确保他们的长期 长期生存。维护复杂主机的路径和过程 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，血液期寄生虫内化细胞膜。 来自外部介质的不渗透分子通过一条 绕过红细胞胞浆。身份识别和 对这一新途径的描述刺激了研究人员 在疟疾研究中寻求新的领域，包括寄生虫转基因， 反义RNA与膜不通透性药物化疗。 基本运输路径的特征将提供 有机会设计战略以中断(或利用)这些过程 损害寄生虫的生存能力。核糖体失活蛋白的来源 植物将被用来研究大分子运输途径和 对其抗疟疾效果进行评估。这些蛋白质被挑选出来 因为它们具有很好的生物化学特性，并产生特定的 体外抗病毒和抗肿瘤细胞毒作用。细胞毒性似乎是 在生物/细胞快速复制的情况下是最好的 就像疟疾和其他传染病的情况一样。这个 核毒素的寄生靶点和细胞毒性基础将是 调查过了。对寄生虫蛋白质和核酸合成的影响 将对DNA稳定性和复制进行研究。取决于他们的 行动模式，结合其他组织的已知复制方案 病原体，这些研究的结果可能会揭示 据此，核毒素可用于治疗疟疾和其他 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.