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是探索任何生物体基本生物学的极有价值的工具。常用的两种工具是RNA干扰和条件表达，这两种方法都没有在疟疾研究中成功实施。我们正在开发一种新的方法来控制疟疾寄生虫分泌途径中的蛋白质。据认为，恶性疟原虫基因组编码的20%以上的蛋白质通过分泌系统到达细胞器或细胞外目的地。这些蛋白在寄生虫代谢、营养获取、入侵、宿主细胞重塑和寄生虫生物学的其他关键方面起着关键作用。本课题的目的是设计和优化一种条件探针来控制恶性疟原虫可溶性分泌蛋白的定位。然后将该方法应用于两个生物靶点进行验证：一个在顶质体细胞器中，另一个在寄生液泡中。条件定位工具的成功开发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

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. PUBLIC HEALTH RELEVANCE: The inevitable rise of drug-resistant malaria parasites creates a continuing need to develop new control strategies. We are developing a genetic tool that will help to probe basic parasite biology and validate new drug targets.