Identifying contexts that improve Wolbachia as a biocontrol of vector-borne disea

描述（由申请人提供）：本提案的主要研究目标是提高沃尔巴克氏体作为媒介传播疾病的生物防治手段的使用。沃尔巴克氏体是母体传播的细菌，存在于节肢动物宿主的细胞中。沃尔巴克氏体通过多种机制对宿主进行生殖操纵，包括细胞质不相容，这减少了未感染的雌性与感染的雄性交配时产生的后代数量。Turelli博士（发起人）和消除登革热小组的其他成员（://www.eliminatedengue.com/）正在使用来自果蝇的沃尔巴克氏体来减少登革热病毒从伊蚊向人类的传播。在自然界成功建立沃尔巴克体-伊蚊关联，有可能减少目前面临感染风险的25亿人中登革热的发生。然而，这需要确定使沃尔巴克氏体感染在宿主人群中传播的环境。通过确定促进沃尔巴克氏体感染传播的生态和遗传背景，以及重要表型背后的遗传因素，申请人的研究将从根本上改善沃尔巴克氏体作为媒介传播疾病生物防治的使用。目标1将确定促进沃尔巴克氏体感染在宿主人群中传播和维持的生态和遗传环境。利用基因组学、显微镜和适应度分析，该目标将评估三方基因组相互作用的功能影响

DESCRIPTION (provided by applicant): The main research objective of this proposal is to improve the use of Wolbachia as a biocontrol of vector-borne disease. Wolbachia are maternally transmitted bacteria that reside in the cells of arthropod hosts. Wolbachia reproductively manipulate their hosts using a variety of mechanisms including cytoplasmic incompatibility, which reduces the number of offspring produced when uninfected females mate with infected males. Dr. Turelli (sponsor) and other members of the Eliminate Dengue Team (://www.eliminatedengue.com/) are using Wolbachia from Drosophila flies to reduce the transmission of the dengue virus from Aedes mosquitoes to humans. Successful establishment of Wolbachia-Aedes associations in nature has the potential to reduce the occurrence of dengue fever in the 2.5 billion people currently at risk of infection. However, this requires the identification of contexts that enable the spread of Wolbachia infections through host populations. By identifying the ecological and genetic contexts that facilitate the spread of Wolbachia infections, and the genetic factors underlying important phenotypes, the applicant's research will fundamentally improve the use of Wolbachia as a biocontrol of vector-borne disease. AIM 1 will identify the ecological and genetic contexts that facilitate the spread and maintenance of Wolbachia infections in host populations. Using genomics, microscopy, and fitness assays, this aim will then evaluate how tripartite genomic interactions functionally impact the strength of reproductive alterations inflicted upon hosts by Wolbachia. AIM 2 will then evaluate the phylogeographic history of Wolbachia infections, and the capacity for rapid coevolution of Wolbachia-host associations. Determining the capacity for rapid coevolution is critical considering that theory predicts that coevolution of Wolbachia-host associations towards mutualism should enable the proliferation of Wolbachia through host populations. The applicant will receive training in cell biology, microscopy, genetics, genomics, and in new systems (i.e., Drosophila suzukii and Aedes aegypti). The sponsor, his collaborators, and the faculty at UC Davis are particularly capable to assist the applicant in achieving his goals. The applicant will build a direct and long-term collaboration with the Eliminate Dengue Team enabling him to work with those on the vanguard of applying Wolbachia as a biocontrol of vector-borne diseases throughout his career as a principal investigator.