Generation of transmission-compromised mosquitoes

传播受限的蚊子的产生

• 批准号: 10039237
• 负责人: Deborah J Andrew
• 金额: $ 24.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-20 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039237
• 关键词: Adult; Aedes; Affect; African Trypanosomiasis; Age; Anopheles gambiae; Automobile Driving; Biological Assay; Blood; CRISPR/Cas technology; Candidate Disease Gene; Cause of Death; Cells; Cessation of life; Child; Clinical; Communicable Diseases; Culicidae; Dengue; Dengue Fever; Dengue Hemorrhagic Fever; Dengue Virus; Disease; Distant; Drops; Drosophila genus; Event; Expression Profiling; Female; Fertility; Generations; Genes; Goals; Head; Homeostasis; Human; Incidence; Individual; Insect Vectors; Insecta; Invaded; Laboratories; Learning; Leishmaniasis; Life Cycle Stages; Link; Longevity; Lyme Disease; Maintenance; Malaria; Morphogenesis; Morphology; Mosquito-borne infectious disease; Mutation; Ocular Onchocerciasis; Organ; Outcome; Parasites; Pathway interactions; Persons; Phenotype; Population; Publications; RNA Interference; Reporting; Role; Saliva; Salivary Glands; Specific qualifier value; Sporozoites; Testing; Time; Tissues; Tube; Virus; Work; ZIKA; base; conditional knockout; cost; disease transmission; feeding; fitness; genetic testing; gland development; human disease; knock-down; malaria infection; pathogen; prevent; transcription factor; transmission process; vector mosquito

Insect-borne diseases kill more humans than all other diseases combined. Existing strategies for limiting the spread of such diseases are helping, but it is clear that complete eradication of some of the most deadly diseases – especially malaria – is going to require additional approaches. The goal of this project is to test strategies to block insect-borne disease transmission by intervening at the level of the insect vector, preventing transmission of disease-causing parasites and viruses by causing the timely death of the adult female mosquito salivary gland (SG). A current limitation for studies attempting to manipulate the SG – a gateway organ for transmitting malaria and other insect borne diseases - is that almost nothing is known about SG development, function or homeostasis in any insect outside Drosophila. The molecules involved in specifying, building or specializing mosquito SGs are largely unknown. The proposed study begins with learning the consequences of RNAi knock-down of three Anopheles gambiae transcription factor (TF) genes whose Drosophila orthologues have key roles in Drosophila SG development, function and survival. We ask if TF gene knockdown affects SG survival or morphology, or the ability of infective malaria sporozoites to invade the SGs and to be transmitted in the saliva. In the second aim, we create null and tissue-specific mutations in the Anopheles gambiae sage gene, which encodes a SG-specific TF whose Drosophila orthologue is required for SG survival and expression of SG-specific cargo genes. We ask how complete loss of sage affects viability, fecundity and SG morphology. We ask if loss of sage affects sporozoite SG invasion and sporozoite counts in saliva. We also determine if SG-specific loss of sage following a blood meal leads to similar outcomes. Finally, to learn how well our SG-centric approach to limiting disease transmission works in general, we ask if RNAi knockdown of the sage orthologue in Aedes aegypti affects the SG and its ability to transmit Dengue virus.

虫媒疾病造成的死亡人数超过所有其他疾病的总和。现有的限制 这类疾病的传播正在起作用，但很明显， 疾病-特别是疟疾-将需要更多的方法。这个项目的目标是测试 通过在昆虫媒介一级进行干预， 通过导致成年雌性及时死亡传播致病寄生虫和病毒 蚊唾液腺（SG）。试图操纵SG的研究的当前限制-网关 传播疟疾和其他昆虫传播疾病的器官-几乎对SG一无所知 在果蝇属以外的任何昆虫中的发育、功能或体内平衡。参与指定的分子， 建造或专门的蚊子SG在很大程度上是未知的。拟议的研究从学习 RNAi敲低三种冈比亚按蚊转录因子（TF）基因的结果， 果蝇直向同源物在果蝇SG发育、功能和存活中具有关键作用。我们问如果TF 基因敲除影响SG存活或形态，或感染性疟疾子孢子侵入 在唾液中传播。在第二个目标中，我们在基因组中创建无效和组织特异性突变。 冈比亚按蚊sage基因，其编码SG特异性TF，其果蝇直向同源物是 SG存活和SG特异性货物基因的表达。我们想知道鼠尾草的完全丧失如何影响生存能力， 生殖力和SG形态。我们想知道sage的缺失是否会影响子孢子SG的侵入和子孢子计数。 口水我们还确定，如果SG特定的损失鼠尾草以下血餐导致类似的结果。 最后，为了了解我们以SG为中心的方法在限制疾病传播方面的效果如何，我们问， RNAi敲低埃及伊蚊sage直系同源基因影响SG及其传播登革热的能力 病毒