Approaches for genetic manipulation of Naegleria fowleri

项目摘要 该提案的目标是开发分子工具和方法，用于研究 致病性自由生活的福氏耐格里阿米巴。目前不存在这些。这个变形虫 是原发性阿米巴脑膜脑炎（PAM）的病原体， 致命的脑部感染缺乏治疗这种感染的有效药物， 需要开发更好的治疗阿米巴感染的药物。缺乏 了解寄生虫的基因功能仍然是靶向药物的主要障碍 发展运动。在这里，我们建议通过开发 通过RNAi和CRISP/Cas9介导的基因编辑进行基因沉默和消融的方法 和转基因表达。这些方法将作为重要的第一步， 了解基因功能和重要性，这是早期药物发现工作的关键。

Project Summary The goal of this proposal is to develop molecular tools and approaches for the study of the pathogenic free-living amoeba Naegleria fowleri. These currently do not exist. This amoeba is the causative agent of primary amebic meningoencephalitis (PAM), an almost invariable lethal brain infection. The lack of useful drugs for the treatment of this infection emphasizes the need to develop better therapeutic agents for amoebae infections. The lack of understanding of gene function in the parasite remains a major hurdle in target-based drug development campaigns. Here, we propose to address this problem by developing approaches for gene silencing and ablation by RNAi and CRISP/Cas9-mediate gene editing and transgene expression. These approaches will serve as an important first step in understanding both gene function and essentiality, key to early-stage drug discovery efforts.