Digestive vacuole biogenesis in the malaria parasite

这项建议旨在了解疟疾寄生虫消化液泡(DV)的生物发生， 恶性疟原虫。这种酸性的溶酶体样细胞器负责降解大的 从宿主红细胞摄取的血红蛋白的量。DV也是最大的行动地点 历史上临床上最有用的抗疟疾药物家族是4-氨基喹啉类药物。尽管 这种细胞器对寄生虫发育和抗疟疾化疗的重要性，目前知之甚少 关于生物合成的寄生虫蛋白质和宿主细胞胞质的成分是如何输送到 DV在红细胞内的生命周期中。我建议确定哪些贩运步骤对于 通过特定阶段的遗传和化学干扰将寄生虫和宿主细胞蛋白运输到DV 细胞内运输。这些研究将使我们能够解决这样的假设，即寄生虫的一个途径 蛋白质向DV的运输依赖于蛋白质分泌和分类的SEC和VPS成分。我们的 第二个主要假设是血红蛋白和一些宿主红细胞胞浆成分的摄取 通过动力蛋白依赖的内吞作用进行。

This proposal aims to understand the biogenesis of the digestive vacuole (DV) of the malaria parasite, Plasmodium falciparum. This acidic, lysosomal-like organelle is responsible for the degradation of large quantities of hemoglobin ingested from the host erythrocyte. The DV is also the site of action of the largest and historically the most clinically useful family of antimalarial drugs, the 4-aminoquinolines. Despite the importance of this organelle to parasite development and antimalarial chemotherapy, little is currently known about how both biosynthetic parasite proteins and components of the host cell cytosol are delivered to the DV during the intraerythrocytic lifecycle. I propose to determine which trafficking steps are essential for the transport of parasite and host cell proteins to the DV by genetic and chemical disruption of defined stages of intracellular transport. These studies will enable us to address the hypothesis that one pathway of parasite protein trafficking to the DV relies upon the Sec and Vps components of protein secretion and sorting. Our second major hypothesis is that uptake of hemoglobin and some host erythrocyte cytosol components proceeds via dynamin-dependent endocytosis.