Species-specific regulated transposition in mosquitoes

描述（由申请人提供）：媒介传播疾病每年在全世界造成超过一百万人死亡。这项研究的长期目标是培育出在遗传上难以传播病原体（如引起疟疾和登革热的病原体）的病媒蚊子菌株。这些昆虫将被用来检验这样一种假设，即使蚊子种群的媒介能力下降的基因或等位基因频率增加将导致该疾病的发病率和流行率降低。在我们的实验室和其他人成功地证明了在蚊子中产生病原体难解表型的工程合成效应基因的可能性之后，我们现在建议研究特定的驱动机制，以促进这些基因在媒介蚊子种群中安全有效地传播。本应用程序的具体目的是利用蚊子转基因的进展和昆虫胚胎发育的基本性质，以满足研究基因驱动机制的需要。具体目的是：1)鉴定冈比亚按蚊纳米（nos）同源基因特异性表达模式的顺式作用DNA和启动子元件；斯氏蚊和埃及伊蚊；2)构建并检测由蚊子nos基因和Mos1、piggyBac转座子组成的合成转座子；3)确定人工转座子是否能在笼养种群中传播。冈比亚和Ae。蚊。

DESCRIPTION (provided by applicant): Vector-borne diseases cause over one million deaths annually in people worldwide. The long term objective of this research is to develop strains of vector mosquitoes that are genetically refractory to the transmission of pathogens such as those that cause malaria and dengue fever. These insects will be used to test the hypothesis that an increase in the frequency of a gene or allele that confers decreased vector competence to a population of mosquitoes will lead to a reduction in the incidence and prevalence of that disease. Following the successful efforts of our laboratory and others demonstrating the possibilities for engineering synthetic effector genes that produce pathogen refractory phenotypes in mosquitoes, we now propose to investigate specific drive mechanisms that would facilitate the safe and efficient spread of such genes in vector mosquito populations. The SPECIFIC AIMS of this application have been designed to take advantage of the progress made with mosquito transgenesis and the fundamental nature of embryonic development in insects, to meet the need to research gene drive mechanisms. The SPECIFIC AIMS are to: 1) Identify the cis-acting DNA and promoter elements responsible for the specific expression patterns of the nanos (nos) orthologous genes in Anopheles gambiae, An. stephensi and Aedes aegypti; 2) Construct and test synthetic transposable elements composed of mosquito nos genes and the Mos1 and piggyBac transposons; and 3) Determine if synthetic transposons can spread in caged populations of An. gambiae and Ae. aegypti.