Disruption of Host-Seeking Behavior in Anopheles Gambiae Mosquitoes using Odorant

描述（由申请人提供）：冈比亚按蚊雌蚊是疟原虫恶性疟原虫极其有效的传播媒介，将这种致命疾病传播给近5亿人，每年造成近75万人死亡。由于蚊子主要依靠嗅觉来寻找人类宿主，因此嗅觉系统是开发阻断蚊子与人类接触策略的主要目标。目前利用蚊子嗅觉系统的控制方法，如在皮肤上涂抹避蚊胺和二氧化碳捕集器等驱蚊剂，由于成本高、直接在皮肤上施用不便以及体积大，对有风险的人群不起作用。该提案的目标是确定价格合理、方便和安全的基于气味的应用，这些应用可以少量使用，以保护一个空间区域，如住所免受按蚊的侵害，并设计低成本的陷阱诱饵。蚊子从远处使用的主要线索之一是呼出气体中的二氧化碳。当蚊子利用二氧化碳羽流靠近时，它也被认为是被皮肤和汗水相关的气味所吸引。在本提案中，我们将重点放在冈比亚按蚊的二氧化碳感应神经元上，作为开发气味介导的行为破坏策略的目标。为此，我们开发了一系列强大的技术，包括神经生理学、化学信息学和行为分析。首先，我们计划研究一项新的观察，即二氧化碳感知神经元也参与检测人体皮肤的气味，可能会引起近距离吸引。由于对皮肤的吸引力知之甚少，我们希望我们的分析能够揭示这一重要行为过程背后的机制。其次，我们计划找出可以模仿二氧化碳嗅觉活动的气味剂，并测试它们作为陷阱有效诱饵的效用。第三，我们建议通过抑制二氧化碳感知神经元或通过“超长时间”激活神经元来识别能够阻止二氧化碳检测的气味剂。这些二氧化碳探测掩蔽气味将测试其保护空间区域的能力，例如小住所

DESCRIPTION (provided by applicant): The female Anopheles gambiae mosquito is an extremely efficient vector for the malarial parasite Plasmodium falciparum and transmits this deadly disease to nearly 500 million people, causing nearly 750,000 deaths every year. Since the mosquito relies primarily on the sense of smell to find a human host, the olfactory system is a prime target for development of strategies to disrupt contact between mosquitoes and humans. Current methods of control that exploit the mosquito olfactory system such as repellents applied to the skin like DEET and CO2-traps are not useful for the population at risk due to high costs, inconvenience of direct skin applications, and bulk. The goal of this proposal is to identify affordable, convenient, and safe odor-based applications that can be used in small quantities to protect a spatial area such as an abode from Anopheles mosquitoes, and design low-cost lures for traps. One of the primary cues that mosquitoes use from a distance is CO2 present in exhaled breath. As the mosquito navigates closer using the CO2 plumes, it is also thought to be attracted to skin and sweat associated odors. In this proposal we focus on the CO2-sensing neuron of Anopheles gambiae as a target for development of odor-mediated behavior disruption strategies. For this purpose we have developed an array of powerful technologies that involve neurophysiology, chemical- informatics, and behavioral analysis. First, we plan to investigate a novel observation that the CO2-sensing neuron is also involved in detecting human-skin odorants, presumably causing close-range attraction. Since little is understood about attraction towards skin, we expect our analyses to reveal mechanisms underlying this important behavioral process. Second, we plan to identify odorants that can mimic the olfactory activity of CO2, and test their utility in acting as efficient lures for traps.And third, we propose to identify odorants that can block detection of CO2 by either inhibiting the CO2-sensing neuron, or by "ultra-prolonged" activation of the neuron. These CO2-detection masking odors will be tested for the ability to protect a spatial area, such as a small abode, from host-seeking Anopheles mosquitoes. Successful completion of this proposal will provide safe and affordable odorants that can reduce contact between humans and Anopheles gambiae mosquitoes.