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改进沃尔巴克氏体作为病媒传播疾病生物防治的使用。沃尔巴克氏体是存在于节肢动物宿主细胞中的母体传播细菌。沃尔巴克氏体利用多种机制繁殖操纵其宿主，包括细胞质不相容性，当未感染的雌性与感染的雄性交配时，细胞质不相容性减少了后代的数量。Turelli博士（发起人）和消灭登革热小组（www.eliminatedengue.com/）的其他成员正在使用果蝇的沃尔巴克氏体来减少登革热病毒从伊蚊传播到人类。在自然界中成功建立沃尔巴克氏体-伊蚊联合体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通过宿主人群传播的环境。 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病媒传播疾病生物防治的用途。AIM 1将确定促进宿主人群中沃尔巴克氏体感染传播和维持的生态和遗传背景。使用基因组学，显微镜，和健身测定，这一目标将评估三方基因组相互作用如何在功能上影响 沃尔巴克氏体对宿主造成的生殖改变的强度。然后，AIM 2将评估沃尔巴克氏体感染的地理历史，以及沃尔巴克氏体-宿主协会快速共同进化的能力。确定快速共同进化的能力是至关重要的，考虑到理论预测，共同进化的沃尔巴克氏体主机协会互利共生应使沃尔巴克氏体通过主机人口的扩散。 申请人将接受细胞生物学，显微镜，遗传学，基因组学和新系统（即，Suzukii和埃及伊蚊）。赞助商，他的合作者和加州大学戴维斯分校的教师特别有能力帮助申请人实现他的目标。申请人将与消灭登革热小组建立直接和长期的合作，使他能够在其作为主要研究者的职业生涯中与那些将沃尔巴克氏体作为病媒传播疾病生物防治的先锋合作。

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.