Species-specific regulated transposition in mosquitoes

描述(申请人提供)：病媒传播的疾病每年导致全球100多万人死亡。这项研究的长期目标是培育出在遗传上对疟疾和登革热等病原体的传播具有抵抗力的媒介蚊子品系。这些昆虫将被用来检验一种假设，即导致蚊子种群媒介能力下降的基因或等位基因的频率增加，将导致这种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改造合成效应基因在蚊子中产生病原体耐药表型的可能性之后，我们现在提议研究特定的驱动机制，以促进此类基因在媒介蚊子种群中安全和有效地传播。这一应用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。其具体目的是：1)确定冈比亚按蚊Nanos(Nos)正源基因特定表达模式的顺式作用DNA和启动子元件。2)构建和测试由蚊子nos基因和Mos1和iggyBac转座子组成的合成转座元件；以及3)确定合成转座子是否可以在笼养的蚊子种群中传播。冈比亚亚纲和Ae.埃及伊蚊。

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.