Molecular Mechanism of Cytoplasmic Incompatibility in Mosquitoes

蚊子细胞质不相容的分子机制

• 批准号: 7788302
• 负责人: Zhiyong Xi
• 金额: $ 19万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2012-01-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788302
• 关键词: Adult; Aedes; Ankyrins; Bacteria; Computer Simulation; Consensus; Culex (Genus); Culicidae; Dengue; Development; Disease Resistance; Drosophila melanogaster; Embryo Deaths; Embryonic Development; Failure; Female; Fertilization; Gene Expression; Genes; Genetic; Genome; Goals; Human; Infection; Integration Host Factors; Malaria; Mediating; Methods; Modeling; Modification; Molecular; Mosquito-borne infectious disease; Ovary; Partner in relationship; Pathway interactions; Phenotype; Population; Proteins; RNA Interference; Refractory; Research; Sequence Homology; Spermatogenesis; System; Tertiary Protein Structure; Testing; Testis; Tissues; Transgenes; Transgenic Organisms; West Nile virus; Wolbachia; Work; base; biological systems; egg; functional genomics; genome sequencing; improved; innovation; knock-down; male; pathogen; protein protein interaction; public health relevance; reproductive; response; sperm cell; transmission process; zygote

DESCRIPTION (provided by applicant): The endosymbiotic bacterium Wolbachia is widely recognized for its potential as a vehicle to introduce disease-resistance genes into mosquitoes, making them refractory to the human pathogens they transmit. This is due to its ability to induce a reproductive abnormality known as cytoplasmic incompatibility (CI). CI is early embryo death when a Wolbachia infected male mates with a female that is uninfected or harboring a different Wolbachia type. Since uninfected males can successfully mate with infected females, Wolbachia and any gene it carries can spread quickly in a population. First discovered in the Culex mosquito, CI is the only phenotype known to be induced by Wolbachia in mosquito. Although different models has been developed to interpret the CI mechanisms, the molecular base for CI is not yet elucidated. We had successfully generated a stable Wolbachia infection in an Aedes aegypti line. Due to the ability of Wolbachia to induce the complete CI in this line and the availability of whole genome sequence in Ae. aegypti, this Wolbachia/mosquito association provides us an ideal system to dissect the CI mechanism. Our long term goal is to understand the cross talk between Wolbachia and its host which results in the occurrence of CI. Our central hypothesis is that CI is induced by a change in the expression of genes involved in spermatogenesis in testes and embryogenesis in ovaries. Our project has three specific aims: 1) Construct an in silico Wolbachia-mosquito protein interactions network. We will predict Wolbachia-mosquito protein interaction network by computation methods based on protein domain profiles and sequence homology. 2) Define the response of mosquito genes in reproductive tissues to Wolbachia infection. We will use microarray to compare the gene expression in ovaries and testes between Wolbachia-infected and uninfected mosquitoes. 3) Identify host factors that determine CI expression. We will knock-down the putative host CI genes by RNA interference and test their impact on CI expression. This research is innovative because it is the first study of the CI mechanisms at the systems biological and functional genomic level. The successful completion of this project will uncover host factors that determine CI, which can be used for further identification of their interaction partners in Wolbachia. Our anticipated findings would also contribute directly to the current effort to improve the Wolbachia-based transgene driver system to spread genes capable of blocking the transmission of mosquito-borne pathogens. PUBLIC HEALTH RELEVANCE: Our anticipated findings would aid in the development of the improved genetic methods to block the transmission of mosquito-borne infectious diseases, including malaria, dengue fever and West Nile.

描述（由申请人提供）：内共生细菌Wolbachia因其作为将抗病抗性基因引入蚊子引入蚊子的潜力而被广泛认可，使其对传播的人类病原体难治性。这是由于其能够诱导被称为细胞质不相容性（CI）的生殖异常的能力。 CI是早期的胚胎死亡，当时沃尔巴氏菌感染了未感染或包含不同沃尔巴氏菌类型的雌性的男同伴。由于未感染的雄性可以成功与受感染的女性交配，因此沃尔巴奇及其携带的任何基因都可以在人群中迅速传播。 CI最初是在Culex蚊子中发现的，它是沃尔巴奇在蚊子中诱导的唯一表型。尽管已经开发出不同的模型来解释CI机制，但尚未阐明CI的分子基础。我们成功地在埃及埃及线上成功产生了稳定的沃尔巴奇感染。由于Wolbachia能够在这条线中诱导完整的CI以及AE中整个基因组序列的可用性。埃及，这种沃尔巴基亚/蚊子协会为我们提供了剖析CI机制的理想系统。我们的长期目标是了解Wolbachia及其宿主之间的串扰，从而导致CI发生。我们的中心假设是，CI是由睾丸中与精子发生的基因表达的变化所诱导的，而卵巢中的胚胎发生。我们的项目具有三个特定的目的：1）在沃尔巴乔 - 摩斯奎托蛋白相互作用网络中构建一个。我们将通过基于蛋白质域谱和序列同源性的计算方法来预测Wolbachia-mosquito蛋白质相互作用网络。 2）定义生殖组织中蚊子基因对沃尔巴奇感染的反应。我们将使用微阵列比较卵巢中的基因表达和沃尔巴契亚感染和未感染的蚊子之间的睾丸。 3）确定确定CI表达的宿主因素。我们将通过RNA干扰敲低推定的宿主CI基因，并测试其对CI表达的影响。这项研究具有创新性，因为它是系统生物学和功能基因组水平上CI机制的首次研究。该项目的成功完成将发现确定CI的宿主因素，该因素可用于进一步识别其在沃尔巴基亚的相互作用伙伴。我们预期的发现还将直接有助于当前的努力，以改善基于沃尔巴奇的转基因驱动系统，以传播能够阻止蚊子传播病原体传播的基因。 公共卫生相关性：我们的预期发现将有助于开发改进的遗传方法，以阻止包括疟疾，登革热和西尼罗河在内的蚊子传播传染病的传播。