The Plastid of Toxoplasma gondii

性状（申请人提供）：弓形虫是一种重要的 机会致病菌，导致弓形虫脑炎发作， 大约每13个人中就有一个死于艾滋病。 大约3%的艾滋病毒阳性个体最初表现为 弓形虫病这种寄生虫拥有一种独特的细胞器叫做顶质体， 其在遗传和功能上与质体如叶绿体相关。 由于人类宿主缺乏类似的细胞器，顶质体被认为是 是抗寄生虫药物开发的重要潜在靶点 剂.然而，对这些细胞的功能和生物起源知之甚少。 顶质体该提案概述了旨在表征 蛋白质靶向顶质体的机制。我们和其他人已经 最近表明，蛋白质的目的地为基质的T。弓形虫质体 最初进入寄生虫分泌系统，然后被路由到 质体我们已经产生了三种向顶质体运输的模型， 将在拟议的研究中进行测试。我们将利用配体调节的 聚集来检查蛋白质从内质网到 顶质体我们还将鉴定顶质体膜标记蛋白， 从生物化学和遗传学的角度来研究。拟议的实验将 提供了进一步的了解顶质体的生物起源及其 对T的重要性弓形虫和相关病原体。

DESCRIPTION (Provided by the applicant): Toxoplasma gondii is an important opportunistic pathogen, causing an episode of toxoplasmic encephalitis in approximately one of every thirteen individuals succumbing to AIDS. Approximately 3 percent of individuals HIV positive initially present with toxoplasmosis. The parasite possesses a unique organelle called the apicoplast, which is genetically and functionally related to plastids such as chloroplasts. Because the human host lacks a similar organelle, the apicoplast is thought to represent an important potential target for the development of anti-parasitic agents. Little is known, however, about the function and biogenesis of the apicoplast. This proposal outlines experiments aimed at characterizing the mechanisms by which proteins are targeted to the apicoplast. We and others have recently shown that proteins destined for the stroma of the T. gondii plastid initially enter the parasite secretory system and then are routed to the plastid. We have generated three models of trafficking to the apicoplast that will be tested in the proposed studies. We will exploit ligand- regulated aggregation to examine the flow of proteins from the endoplasmic reticulum to the apicoplast. We will also identify an apicoplast membrane marker protein and study it at the biochemical and genetic level. The proposed experiments will provide additional insight into the biogenesis of the apicoplast and its importance to T. gondii and related pathogens.