Receptors and channels controlling sensation and behavior in Aedes aegypti

埃及伊蚊等蚊子是疾病的传播媒介，它们依靠敏锐的感官来定位人类宿主， 以及寻找同类，以便交配。然而，我们对这一问题只有一个初步的了解。 控制这些关键行为的受体。这项研究的目的是解决这一差距。找到 人类宿主，女性艾氏原住民埃及整合来自不同刺激的信息，包括CO2，视觉线索，有机 分子和皮肤温度。我们发现了另一个线索。目标1建立在我们的初步数据基础上， AE.埃及伊蚊使用红外（IR）辐射作为额外的宿主刺激。我们概述了揭示IR感受神经元和检测IR的受体的实验。为了实现这一目标，我们设计了一种高效的行为 用于监测IR吸引的测定，以及一种新的分子遗传学方法来治疗旁路并发症， 结合多种遗传元素。Aim 2利用了我们最近在TRP中创建的一个突变 通道，使男性和女性失聪。我们将在swarm中测试这个通道和听觉的作用 形成，交配和寻找人类宿主我们提出的实验将质疑圣像崇拜的想法， 蚊子会被人类的语言所吸引这将是一个特别具体的线索，以帮助他们 识别并瞄准人们。在目标3中，我们提出了一项新的战略，以克服一个主要障碍 限制了昆虫不育技术（SIT）的功效。SIT是抑制Ae的有希望的策略。埃及人它 包括用不育的雄性淹没当地人口，这使得雌性在交配时不育。然而，在这方面， 持久抑制蚊子种群的一个障碍是野生型雄性蚊子在竞争中胜过不育蚊子 男性。我们提出了两种互补的方法来显着提高男性交配成功。这项工作 具有转化SIT的潜力，从而有效地抑制Ae。埃及人。目标4涉及另一个关键 感觉问题-识别驱避剂的受体。我们最近发现视紫红质的功能 作为多模式的感觉受体，挑战了100年来他们只检测光的教条。这里我们 建议测试的假设，视蛋白在Ae。埃及伊蚊作为天然存在的驱虫剂的高度敏感的受体发挥作用。如果我们提出的实验得到证实，这将表明视蛋白 包括一类新的、未被怀疑的嗅觉受体。为了实现我们的目标，我们将承担一个 广泛的最先进的方法，其中一些是我们专门为此开发的 项目其中包括新的分子遗传工具，一套行为分析，原始视频跟踪 软件和几种类型的电生理记录。总之，这个项目的统一主题是 确定蚊子感知人类宿主的难以捉摸的受体和机制， 同种的配偶从这项工作中收集到的见解具有令人兴奋的潜力，可以导致创新战略 控制Ae。埃及，并减少昆虫传播的疾病。

Mosquitoes such as Aedes aegypti are disease vectors that rely on their keen senses to locate human hosts, and for finding conspecifics, so that they can mate. However, we have only a rudimentary understanding of the receptors that control these critical behaviors. The goal of the proposed research is to address this gap. To find human hosts, female Ae. aegypti integrate information from diverse stimuli, including CO2, visual cues, organic molecules, and skin temperature. We have discovered another cue. Aim 1 builds on our preliminary data that Ae. aegypti use infrared (IR) radiation as an additional host stimulus. We outline experiments to reveal the IR-sensing neurons, and the receptor that detects IR. To pursue this aim, we devised a highly effective behavioral assay for monitoring IR attraction, and a new molecular genetic approach to bypass complications in combining multiple genetic elements. Aim 2 takes advantage of a mutation that we recently created in a TRP channel, which renders males and females deaf. We will test the roles this channel and hearing in swarm formation, mating and in finding human hosts. Our proposed experiments will interrogate the iconoclastic idea that mosquitoes are attracted to human speech. This would be a particularly specific cue to help them recognize and zero in on people. In Aim 3, we propose a new strategy to overcome a major impediment limiting the efficacy of the sterile insect technique (SIT). SIT is a promising strategy to suppress Ae. Aegypti. It involves inundating a local population with sterile males, which render females sterile upon mating. However, an impediment to lasting suppression of mosquito populations is that wild-type males outcompete the sterile males. We propose two complementary approaches to significantly elevate male mating success. This work has the potential to transform SIT, and thereby effectively suppress Ae. aegypti. Aim 4 concerns another key sensory issue—identification of the receptors for repellents. We recently discovered that rhodopsins function as multi-modal sensory receptors, challenging 100 years of dogma that they detect only light. Here, we propose to test the hypothesis that an opsin in Ae. aegypti functions as a highly sensitive receptor for naturally-occurring insect repellents. If confirmed by our proposed experiments, this would demonstrate that opsins comprise a new, unsuspected class of olfactory receptor. To accomplish our goals, we will bring to bear an extensive repertoire of state-of-art approaches, some of which we have developed specifically to pursue this project. These include new molecular genetic tools, a suite of behavioral assays, original video tracking software, and several types of electrophysiological recordings. In summary, the unifying theme in this project is the identification of elusive receptors and mechanisms through which mosquitoes sense human hosts and conspecific mates. The insights gleaned from this work have exciting potential to lead to innovative strategies to control Ae. aegypti, and reduce insect-borne disease.