Ionotropic Receptor Function in Anopheles gambiae

项目总结/摘要 蚊子是从疟疾到登革热、寨卡病毒和疟疾等广泛传播的人类疾病的重要媒介。 基孔肯雅热，温度和湿度检测对支持蚊子生存至关重要， 繁殖和寻找宿主准确感知环境温度对于维护 最佳体温，而感知湿度对于避免干燥很重要。温度和 湿度也是寻找寄主和吸血重要线索，湿度对产卵也很重要 因为蚊子幼虫是水生的。但是，尽管它们很重要，热- 蚊子的湿度感应仍然是未知的。 Garrity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 和果蝇的湿度感应。这些受体是保守的载体 蚊子和高度表达在他们的触角，一致的概念，他们提供类似的感官 角色冈比亚按蚊是疟疾的主要传播媒介， 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战略提供关键见解， 对其他媒介蚊子类似机制的潜在影响。 在我的初步研究中，我在冈比亚按蚊中使用了CRISPR/Cas9基因组编辑， 在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学研究，以确定这些受体在 冈比亚按蚊的温度和湿度感应。我的工作将致力于研究 这些受体在蚊子和探测其潜在的作用，在主机寻求行为。

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.