Identification and disruption of mosquito heme transporters

蚊子血红素转运蛋白的鉴定和破坏

• 批准号: 8808360
• 负责人: Zach N. Adelman
• 金额: $ 23.4万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-10 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8808360
• 关键词: Adult; Aedes; Anopheles Genus; Arboviruses; Arthropods; Biliverdine; Binding; Biological Models; Blood; Caenorhabditis elegans; Carrier Proteins; Cell physiology; Cells; Chemicals; Chikungunya virus; Culicidae; Cytosol; Data; Dengue; Development; Digestion; Drosophila genus; Employee Strikes; Endocytosis; Equilibrium; Evolution; Excretory function; Ferritin; Fertility; Free Radicals; Gastrointestinal tract structure; Gene Targeting; Genes; Genetic; Genome; Globin; Golgi Apparatus; Heme; Heme Iron; Hemolymph; High-Throughput Nucleotide Sequencing; Homeostasis; Homologous Gene; Human; Insecta; Integral Membrane Protein; Intervention; Iron; Iron Overload; Lead; Mediating; Micronutrients; Midgut; Mitochondria; Modeling; Molecular; Mutation; Nature; Nematoda; Oogenesis; Orthologous Gene; Pharmaceutical Preparations; Physiological; Plants; Process; Production; Property; Protein Import; Proteins; Reactive Oxygen Species; Regulation; Reporter; Resources; Respiration; Role; Signaling Molecule; Site; Structure; Surface; System; Technology; Tissues; Transcriptional Activation; Transferrin; Transgenic Organisms; Transport Process; Vaccines; Validation; Vertebrates; Yeasts; Yellow Fever; Zebrafish; base; cationic antimicrobial protein CAP 37; disease transmission; egg; heme 1; heme biosynthesis; high reward; high risk; inhibitor/antagonist; insight; iron deficiency; neutralizing antibody; novel; oxidative damage; prevent; public health relevance; research study; success; transcriptome sequencing; uptake; vector; vector mosquito

DESCRIPTION (provided by applicant): Aedes aegypti is the main vector of dengue, yellow fever and chikungunya viruses, and is a model system for studies of other mosquitoes that vector arboviruses. The acquisition of a bloodmeal is by nature a high-risk, high reward activity for the mosquito- virtually unlimited resources to fuel egg production, combined with extraordinarily high levels of iron which must be detoxified to prevent free-radical production and oxidative damage. In contrast, blood-derived iron is both an essential micronutrient for egg production and development as well as a critical signaling molecule to initiate the vitellogenic process. Thus, a fine balance exists between iron overload and iron deficiency, achieved through a highly structured system of iron import, export and storage. In this proposal, we aim to identify and disrupt mosquito transport proteins involved in the cellular uptake of both molecular iron and heme using a combination of high-throughput sequencing (aim 1) and targeted gene editing (aim 2) technologies. The identification of mosquito iron import proteins would provide unique targets for vaccine, drug, or transgenic strategies aimed at disrupting mosquito vectorial capacity, as critical importers/exporters present on the lumenal surface of the digestive tract would be exposed to potential chemical inhibitors or neutralizing antibodies if present in the bloodmeal.

描述（由申请人提供）：埃及伊蚊是登革热、黄热病和基孔肯雅病毒的主要媒介，是研究其他传播虫媒病毒的蚊子的模型系统。从本质上讲，获取血食对蚊子来说是一种高风险、高回报的活动——几乎是无限的资源来为产卵提供燃料，再加上极高水平的铁，必须被解毒以防止自由基的产生