Conditional probes of secretory protein function in malaria parasites

描述(由申请人提供)：控制蛋白质水平的遗传方法对于探索任何生物体的基本生物学都是非常有价值的工具。两种常用的工具是RNA干扰和条件表达，这两种工具都没有在疟疾研究中成功实施。我们正在开发一种新方法来控制疟疾寄生虫分泌途径中的蛋白质。恶性疟原虫基因组编码的蛋白质中，超过20%被认为在到达细胞器或细胞外目的地的途中通过分泌系统。这些蛋白质在寄生虫的新陈代谢、营养获取、入侵、宿主细胞重塑和寄生虫Biolog的其他关键方面发挥着关键作用。本项目的目的是设计和优化一种条件探针来控制恶性疟原虫中可溶性分泌蛋白的定位。然后，将通过将该方法应用于两个生物目标来验证该方法：一个在质外体细胞器中，另一个位于寄生虫液泡中。成功开发有条件的本地化工具将增强我们探索疟疾寄生虫基本生物学的能力，并将使我们能够验证潜力 治疗干预的靶点。

DESCRIPTION (provided by applicant): Genetic methods to control protein levels are extremely valuable tools for probing the basic biology of any organism. Two commonly employed tools are RNA interference and conditional expression, neither of which has been successfully implemented in malaria research. We are developing a new method to control proteins in the secretory pathway of malaria parasites. Over 20% of the proteins encoded by the Plasmodium falciparum genome are thought to pass through the secretory system on their way to organellar or extracellular destinations. These proteins have key roles in parasite metabolism, nutrient acquisition, invasion, host cell remodeling, and other critical aspects of parasite biolog. The goal of this project is to design and optimize a conditional probe to control the localization f soluble secretory proteins in P. falciparum. This method will then be validated by applying it to two biological targets: one in the apicoplast organelle and one which resides in the parasitophorous vacuole. Successful development of a conditional localization tool will enhance our ability to probe the basic biology of malaria parasites and will allow us to validate potential targets for therapeutic intervention.