权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Guy1-conferred female lethality: mechanism and application for mosquito control

Guy1赋予女性致死性：蚊子控制机制及应用

基本信息

批准号：
9221238
负责人：
Zhijian Jake Tu
金额：
$ 39.44万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-09 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9221238
关键词：
Alleles Anopheles Genus Biology Blood Bombyx mori Caenorhabditis elegans Cost of Illness Culicidae DNA Binding DNA Binding Domain Data Dosage Compensation (Genetics)Drosophila melanogaster Embryo Embryonic Development Ensure Female Fertility Gene Expression Generations Genes Genetic Genetic Transcription Genomics Genotype Goals Heterozygote Individual Initiator Codon Insecta Insecticide Resistance Laboratories Lead Link Malaria Measures Methods Molecular Mosquito Control Mosquito-borne infectious disease Nature Nonsense Codon Open Reading Frames Partner in relationship Pathway interactions Pharmaceutical Preparations Phenotype Point Mutation Population Production Property Proteins Province Refractory Regulation Reproduction Resources Sex Behavior Sex Functioning Sex Ratio Siblings Signal Pathway Spermatogenesis Sterility Synthetic Genes Techniques Testing Time Transgenes Transgenic Organisms Y Chromosome combat cost effective disease transmission disorder control feeding gene product genetic approach hatching improved interest knock-down loss of function male mating behavior novel novel strategies pathogen practical application public health relevance reproductive sex sex determination sexual debut vector

项目摘要

DESCRIPTION (provided by applicant): Anopheles mosquitoes are the primary vectors of malaria, one of humankind's most deadly and costly diseases. Malaria control measures are under increasing threat as drug- and insecticide- resistance spreads. Recently developed genomic resources and genetic methods provide unprecedented opportunities to improve our understanding of mosquito biology and develop new strategies to combat malaria and other mosquito-borne diseases. Y chromosome remains unexplored in Anopheles mosquitoes despite its importance in male determination and other aspects of male biology. Since blood feeding and, consequently, the transmission of disease pathogens is the sole province to female mosquitoes, it is critical to release only males when implementing genetic approaches for reducing mosquito populations or for replacing competent vector populations with populations that are refractory to disease transmission. Overcoming technical bottlenecks, we have recently uncovered four Y genes in An. stephensi. Among these, Guy1 is the best candidate for the male-determining M factor. Multiple Guy1-expressing transgenic lines were generated, which produced 6520 transgenic males and 0 transgenic females over multiple generations. Our preliminary data also suggest that the observed 100% female lethality in the Guy1 transgenic An. stephensi may result from mis-regulation of dosage compensation. Importantly, three known master switches of sex-determination, sex-lethal, Fem/Masc, xo-lethal 1, also directly or indirectly regulate dosage compensation in Drosophila melanogaster, Bombyx mori, and Caenorhabditis elegans, respectively. Loss of function sex- lethal alleles and knockdown of the target of Masc cause female embryonic lethality in D. melanogaster and B. mori, respectively. Here, we will test the hypothesis that the An. stephensi Guy1 is a master regulator of either sex-determination or dosage compensation or both. We will pursue the following specific aims: 1) To determine whether Guy1 controls dosage compensation and/or sex-determination; 2) To delineate the molecular mechanism underlying Guy1 function; and 3) To exploit Guy1 transgenics as a means for sex separation and population reduction in Anopheles mosquitoes.