Research Starter Grant: Investigating the biochemical function of Wolbachia pipientis type IV effectors

研究启动资助：研究 Wolbachia pipientis IV 型效应子的生化功能

• 批准号: 1219659
• 负责人: Irene Newton
• 金额: $ 4.77万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1219659&HistoricalAwards=false
• 关键词: Research; Starter; Grant; Investigating; biochemical

The ultimate goal of this project is to identify mechanisms by which an extraordinarily widespread, intracellular bacterium modifies host cell biology. Specifically, this project focuses on the intracellular bacterium Wolbachia and the identification of bacterial determinants that manipulate eukaryotic cell biology. This project leverages the power of bioinformatics and the yeast genetic system to study this unculturable, genetically intractable bacterium. First, the project focuses on proteins, identified in a bioinformatics screen, likely secreted by Wolbachia during the process of host infection. These proteins are characterized in the context of the eukaryotic cell using high-throughput genetic screens and functional genomic approaches including the identification of genetic and biochemical interactions.Identification of the mechanisms by which Wolbachia interacts with its host will contribute to the understanding of this symbiosis in the context of insect vector control. Wolbachia pipientis infects an extremely broad array of eukaryotic hosts, including the mosquito disease vectors Aedes and Anopholes, and have become noteworthy of late due to their specific relevance to these insects. Dengue fever and its more virulent form hemorrhagic fever, are emerging as serious public health threats in the 21st century and controlling the principal vector mosquito is predicted to be critical to the effective prevention of an epidemic. Interestingly, infection by Wolbachia has been shown to prevent transmission of Dengue by Aedes, although the biological mechanisms through which the infection is accomplished are unknown. By characterizing Wolbachia proteins that interact with eukaryotic cell biology, we can better understand the mechanism behind the Aedes-Dengue-Wolbachia interaction, allowing us to better predict how Wolbachia infection may be used to prevent the transmission of diseases by mosquitos. Additionally, because Wolbachia infect such a broad diversity of insects, results from this work will lead to comparative analyses in other infections.

该项目的最终目标是确定一个非常广泛的细胞内细菌修饰宿主细胞生物学的机制。具体而言，该项目的重点是细胞内细菌，并鉴定了操纵真核细胞生物学的细菌决定因素。 该项目利用生物信息学和酵母遗传系统的力量来研究这种不可养殖的，遗传性的细菌。 首先，该项目的重点是在宿主感染过程中沃尔巴奇分泌的生物信息学筛查中鉴定出的蛋白质。 这些蛋白质在真核细胞的背景下使用高通量遗传筛选和功能性基因组方法，包括鉴定遗传和生化相互作用。识别沃尔巴基亚与宿主相互作用的机制将有助于在昆虫载体控制的背景下对这种同源的理解有助于其宿主的相互作用。 Wolbachia pipientis感染了非常广泛的真核宿主，包括蚊子疾病媒介和肛管，并且由于它们与这些昆虫的特定相关性而引起了人们的注意。 登革热及其更具毒性的出血性热，正出现在21世纪的严重公共卫生威胁中，控制主要矢量蚊子对于有效预防流行病至关重要。 有趣的是，尽管未知感染的生物学机制尚不清楚，但沃尔巴氏菌感染已被证明可以防止伊蚊传播登革热。 通过表征与真核细胞生物学相互作用的Wolbachia蛋白，我们可以更好地理解Aedes-Denge-Dengue-Wolbachia相互作用的机制，从而使我们能够更好地预测如何使用Wolbachia感染来防止通过蚊子传播疾病。 此外，由于沃尔巴奇感染了如此广泛的昆虫，因此这项工作的结果将导致其他感染的比较分析。