The molecular and cellular basis of short-range host cue sensing in mosquito vectors

项目总结/摘要 苔藓病的传播依赖于昆虫以人类宿主为食的能力，这种行为是由宿主驱动的， 相关的感官线索温度和湿度是关键的短期线索，促进最后阶段的 宿主接近和叮咬，但人们对蚊子对宿主的反应的分子和细胞基础知之甚少 这些线索，或者这些机制是否在进化上遥远的蚊子中保守。 我们建议解决这些知识差距：1）探索分子基础和进化保守性 疟疾媒介冈比亚按蚊（Anopheles gambiae）之间的热寻求（An.冈比亚）和登革热病媒伊蚊 埃及伊蚊（Ae.埃及）。2)调查蚊子湿度的分子和细胞基础（尚不清楚） 在一个感觉。冈比亚。我们建议通过三个目标实现这些目标： 目的1）探讨趋热机制的演化守恒性。苔藓吸血 被认为有一个共同的进化起源，但控制热寻求的机制是否 在蚊子中的保守性是一个悬而未决的问题。我们将通过比较钥匙的作用来检验这种守恒性。 在多种蚊子中与热寻求有关的受体，以揭示是否以及以何种方式 各种病媒蚊子都有寻找热量的机制。 目的2）确定候选湿度受体表达神经元的感觉特异性 在安。冈比亚。尽管蚊子对湿度的感知对于寻找宿主很重要，但它在很大程度上尚未被探索。 我们将测试蚊子湿度传感器依赖于感受器的亲属的假设， 果蝇体内的湿度我们将研究表达这些信号的感觉神经元的刺激敏感性。 受体，并测试这些受体在检测感官刺激中的作用。 目的3）建立候选潮霉素An的行为学模型。冈比亚。我们将测试我们的 湿度和温度的候选受体有助于蚊子的行为反应 湿度和温度，以及寻找宿主和吸血。我们还将比较如何主机寻找 作用涉及帮助调节体温和水合状态的稳态作用。 这项工作将确定分子受体和感觉神经元，检测温度和湿度， 媒介蚊子，并确定它们在蚊子寻找宿主和吸血中的作用。因为这些行为 支持疾病传播，这些基础科学发现对病媒控制工作具有潜在的相关性。

PROJECT SUMMARY/ABSTRACT Mosquito disease transmission relies on the insect’s ability to feed on human hosts, a behavior driven by host- associated sensory cues. Temperature and humidity are key short-range cues that promote the final stages of host approach and biting, but little is known about the molecular and cellular basis of mosquito responses to these cues, or whether these mechanisms are conserved among evolutionarily distant mosquitoes. We propose to address these knowledge gaps by: 1) Probing the molecular basis and evolutionary conservation of heat-seeking between the malaria vector Anopheles gambiae (An. gambiae) and the dengue vector Aedes aegypti (Ae. aegypti). 2) Investigating the (as yet unknown) molecular and cellular basis of mosquito humidity sensation in An. gambiae. We propose to achieve these goals in three aims: Aim 1) Probe the evolutionary conservation of heat seeking mechanisms. Mosquito blood-feeding is thought to have a common evolutionary origin, but whether the mechanisms that control heat-seeking are conserved across mosquitoes is an open question. We will test this conservation by comparing the roles of key receptors implicated in heat-seeking in multiple mosquito species in order to reveal whether and in what ways heat-seeking mechanisms are shared across vector mosquitoes. Aim 2) Determine the sensory specificities of candidate humidity receptor-expressing neurons in An. gambiae. Despite its importance for host seeking, mosquito humidity sensing is largely unexplored. We will test the hypothesis that mosquito humidity sensors rely on relatives of receptors important for sensing humidity in Drosophila. We will examine the stimulus sensitivities of the sensory neurons expressing these receptors and test the role(s) of these receptors in detecting sensory stimuli. Aim 3) Establish the behavioral roles of candidate hygroin An. gambiae. We will test how our candidate receptors for humidity and temperature contribute to the mosquito’s behavioral responses to humidity and temperature, as well as host seeking and blood feeding. We will also compare how host-seeking roles relate to homeostatic roles in helping modulate body temperature and hydration state. This work will identify molecular receptors and sensory neurons that detect temperature and humidity in vector mosquitoes and establish their roles in mosquito host seeking and blood feeding. As these behaviors supports disease transmission, these basic science findings have potential relevance for vector control efforts.