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

项目摘要/摘要 蚊子疾病的传播依赖于昆虫以人类宿主为食的能力，这一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，它们促进了 寄主接近和叮咬，但对蚊子对蚊子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相距遥远的蚊子中保守。 我们建议通过以下方式解决这些知识空白：1)探索分子基础和进化守恒 在疟疾媒介冈比亚按蚊(Anopheles冈比亚ae(An.冈比亚)和登革热媒介伊蚊 Aegypti(Ae.埃及文)。2)调查蚊子湿度的分子和细胞基础(尚不清楚) 在一种感觉上。冈比亚亚目。我们建议通过三个目标实现这些目标： 目的1)探讨热搜寻机制的进化守恒性。蚊子吸血 被认为有共同的进化起源，但控制寻热的机制是否 在蚊子中保存是一个悬而未决的问题。我们将通过比较key的角色来测试这一守恒性 在多种蚊子物种中参与热寻找的受体，以揭示是否以及以何种方式 媒介蚊子之间共享寻找热量的机制。 目的2)确定候选湿度感受器表达神经元的感觉特异性 在一个。冈比亚亚目。尽管蚊子湿度感应对寻找宿主很重要，但它在很大程度上还没有被探索过。 我们将验证这样的假设，即蚊子的湿度传感器依赖于对感知至关重要的受体的亲属。 果蝇体内的湿度。我们将检查表达这些的感觉神经元的刺激敏感性。 并测试这些受体在检测感官刺激中的作用(S)。 目的3)确定候选潮蛋白AN的行为作用。冈比亚亚目。我们将测试我们的 湿度和温度的候选受体有助于蚊子对 湿度和温度，以及寻找寄主和取血。我们还将比较寻找宿主的方式 作用与帮助调节体温和水合状态的动态平衡作用有关。 这项工作将识别分子感受器和感觉神经元，这些感觉神经元可以检测温度和湿度 传播蚊子，并确定它们在寻找蚊子宿主和觅血方面的作用。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.