The Plastid of Toxoplasma gondii

描述(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。 约3%的HIV阳性患者最初存在 弓形虫病。这种寄生虫拥有一种独特的细胞器，称为顶生质体， 它在基因和功能上与叶绿体等叶绿体相关。 因为人类宿主缺乏类似的细胞器，所以顶生质体被认为 代表着抗寄生虫发展的一个重要潜在目标 探员们。然而，人们对该蛋白的功能和生物发生知之甚少。 质外体。这项提案概述了旨在表征 蛋白质被定位于质外体的机制。我们和其他人有 最近发现，定位于弓形虫质体基质的蛋白质 最初进入寄生虫的分泌系统，然后被路由到 叶绿体。我们已经产生了三种贩运到顶质粒的模型 将在拟议的研究中进行测试。我们将利用配基调控 聚集以检查蛋白质从内质网流向 原生质体。我们还将鉴定一个质外体膜标记蛋白和 从生化和遗传层面进行研究。拟议中的实验将 提供了更多关于质外体的生物发生及其 对弓形虫及相关病原体的重要性。

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.