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100万人死亡。这项研究的长期目标是开发出在遗传上对病原体（如引起疟疾和登革热的病原体）的传播具有抗性的病媒蚊子品系。这些昆虫将被用来检验一种假设，即使蚊子种群的病媒能力降低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。在我们实验室和其他实验室的成功努力证明了在蚊子中产生病原体抗性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的安全和有效传播。本申请的具体目的是利用蚊子转基因所取得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。具体目标是：1）确定冈比亚按蚊nanos（nos）基因特异性表达的顺式作用DNA和启动子元件。stephensi和埃及伊蚊; 2）构建和测试由蚊子nos基因和Mos 1和piggyBac转座子组成的合成转座元件;和3）确定合成转座子是否可以在笼状的An群体中传播。gambiae和Ae.埃及人。

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.