Ionotropic Receptor Function in Anopheles gambiae

冈比亚按蚊的离子型受体功能

• 批准号: 9540145
• 负责人: Chloe Greppi
• 金额: $ 3.04万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9540145
• 关键词: Address; Affect; Afferent Neurons; Air; Alleles; Animals; Anopheles Genus; Anopheles gambiae; Antibodies; Antibody Specificity; Arthropod Vectors; Base Pairing; Behavior; Behavioral; Behavioral Assay; Bite; Blood; Body Temperature; CRISPR/Cas technology; Carbon Dioxide; Cessation of life; Cues; Culicidae; Dengue; Desiccation; Detection; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Esthesia; Family; Frameshift Mutation; Goals; Health; Human; Humidifier; Humidity; Immunohistochemistry; Infection; Insect Vectors; Insecta; Larva; Location; Malaria; Mediating; Molecular; Neurons; Odors; Oviposition; Pattern; Play; Public Health; Reproduction; Role; Sensory; Site; Stimulus; Stream; Temperature; Temperature Sense; Testing; Vector-transmitted infectious disease; Work; Zika Virus; behavior test; behavioral response; behavioral study; chikungunya; experimental study; feeding; fight against; fly; genome editing; human disease; insight; interest; loss of function mutation; member; mutant; receptor; receptor function; response; vector; vector mosquito

Project Summary/ Abstract Mosquitoes are important vectors for widespread human diseases from malaria to dengue, zika virus and chikungunya, and temperature and moisture detection are critical for supporting mosquito survival, reproduction and host-seeking. Accurately sensing environmental temperature is important for maintaining optimal body temperature, while sensing humidity is important for avoiding desiccation. Temperature and humidity are also important cues for host-seeking and blood-feeding, and moisture is important for oviposition as mosquito larvae are aquatic. But despite their importance, the molecular mechanisms underlying thermo- and hygro-sensing in mosquitoes remain largely unknown. Recent work in the Garrity lab has identified key members of a receptor family that modulate cold sensing and moisture sensing in the fruit fly Drosophila melanogaster. These receptors are conserved in vector mosquitoes and highly expressed in their antennae, consistent with the notion that they serve similar sensory roles. Anopheles gambiae is the major vector for malaria and was responsible for over two hundred million infections in 2015. Understanding the molecular mechanisms underlying temperature and humidity sensing in Anopheles gambiae could provide key insights for strategies to control this important disease vector and has potential implications for similar mechanisms in other vector mosquitoes. In my preliminary studies, I have used CRISPR/Cas9 genome editing in Anopheles gambiae to create mutants containing putative loss-of-function mutations in these receptors. I propose to use a combination of electrophysiology, immunohistochemistry and behavioral studies to establish the role(s) of these receptors in thermo- and hygro-sensing in the mosquito Anopheles gambiae. My work will address the sensory function of these receptors in mosquitoes and probe their potential roles in host-seeking behavior.

项目概要/摘要 蚊子是疟疾、登革热、寨卡病毒等广泛人类疾病的重要传播媒介。 基孔肯雅热、温度和湿度检测对于支持蚊子的生存至关重要， 繁殖和寻找寄主。准确感测环境温度对于维持 最佳体温，而感知湿度对于避免干燥很重要。温度和 湿度也是寻找宿主和吸血的重要线索，湿度对于产卵也很重要 因为蚊子的幼虫是水生的。但尽管它们很重要，但热反应背后的分子机制 蚊子的湿度感应仍然很大程度上未知。 加里蒂实验室最近的工作已经确定了调节冷感的受体家族的关键成员 和果蝇果蝇的湿度传感。这些受体在载体中是保守的 蚊子并在其触角中高度表达，这与它们具有相似感官的概念一致 角色。冈比亚按蚊是疟疾的主要传播媒介，导致两亿多人死亡 2015 年感染。了解温度和湿度传感的分子机制 冈比亚按蚊可以为控制这一重要疾病媒介的策略提供重要见解，并已 对其他媒介蚊子中类似机制的潜在影响。 在我的初步研究中，我使用 CRISPR/Cas9 基因组编辑冈比亚按蚊来创建 这些受体中含有推定的功能丧失突变的突变体。我建议结合使用 电生理学、免疫组织化学和行为研究以确定这些受体在 冈比亚按蚊的温度和湿度感应。我的工作将解决感官功能 蚊子体内的这些受体并探讨它们在寻找宿主行为中的潜在作用。