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

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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.