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

描述(由申请人提供)：这项提案的主要研究目标是改进沃尔巴克氏菌作为病媒传播疾病的生物防治的使用。沃尔巴克氏菌是一种通过母体传播的细菌，存在于节肢动物宿主的细胞中。沃尔巴克氏菌通过包括细胞质不亲和性在内的各种机制来繁殖它们的宿主，这种机制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。特雷利博士(赞助商)和消灭登革热团队(www.liminatedengue.com/)的其他成员正在使用果蝇中的沃尔巴克氏菌来减少登革热病毒从伊蚊向人类的传播。成功地建立自然界中的沃尔巴克氏伊蚊协会有可能减少目前有感染风险的25亿人中登革热的发生。然而，这需要确定能够使沃尔巴克氏菌感染通过宿主人群传播的环境。通过确定促进沃尔巴克氏菌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进沃尔巴克氏菌作为病媒传播疾病的生物防治的使用。目标1将确定促进沃尔巴克氏菌感染在宿主人群中传播和维持的生态和遗传背景。利用基因组学、显微镜和适合度分析，这一目标将评估三方基因组相互作用如何在功能上影响 沃尔巴克氏菌对宿主造成的生殖改变的强度。目标2将评估沃尔巴克氏菌感染的系统地理历史，以及沃尔巴克氏菌与宿主之间快速协同进化的能力。考虑到理论预测沃尔巴克氏菌-宿主协会朝着互惠共生的共同进化应该能够通过宿主种群繁殖沃尔巴克氏菌，确定快速共同进化的能力是至关重要的。申请者将接受细胞生物学、显微镜、遗传学、基因组学和新系统(即铃木果蝇和埃及伊蚊)的培训。赞助商、他的合作者和加州大学戴维斯分校的教职员工特别有能力帮助申请者实现他的目标。申请者将与消灭登革热团队建立直接和长期的合作，使他能够在他作为首席研究员的职业生涯中，与那些应用沃尔巴克氏菌作为病媒传播疾病生物控制的先锋合作。

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.