Genetic Analysis of Mosquito Olfactory Preference for Humans

描述（由申请人提供）：本项目的目标是了解登革热蚊子对人类气味强烈偏好的遗传机制。这项拟议中的研究有望（1）深入了解嗅觉行为的分子基础，（2）为预防蚊子传播人类疾病提供有用的具体信息。该实验计划利用了自然蚊子种群之间的比较，这些蚊子种群在嗅觉偏好方面表现出显着差异。一种原始的森林形式的登革热苔藓喜欢非人类动物的气味，而最近进化的一种家养形式强烈喜欢人类的气味。该项目的第一部分（指导）将比较这两种形式的触角，下颚须和大脑转录组，以生成可能调节偏好的候选基因列表。该项目的第二部分（指导）将比较大脑第一处理中心的气味诱发的神经生理活动，以确定宿主气味表征的差异，并生成关于候选人如何通过嗅觉信号级联改变行为的假设。该项目的第三（独立）部分将使用功能和转基因研究的组合来测试特定的假设，即候选化学感受器和其他嗅觉基因的序列和/或表达模式的变化对人类宿主偏好至关重要。这些结果有望为嗅觉偏好的确定方式提供深入了解，并将集中精力开发新的方法来防止蚊子叮咬人类和传播人类疾病。 公共卫生相关性：敏锐的嗅觉帮助昆虫发现疾病并将其传播给数亿人。人类疾病的最致命的昆虫媒介优先被人类的气味吸引，而不是其他动物。该项目旨在揭示蚊子对人类气味的嗅觉偏好的分子基础，并可能有助于开发防止昆虫叮咬人类的新方法。

DESCRIPTION (provided by applicant): The goal of this project is to understand the genetic mechanisms underlying the robust preference of the Dengue Fever Mosquito for human scent. The proposed research promises to (1) provide insight into the molecular basis of olfactory behavior and (2) provide specific information useful for preventing the spread of human disease by mosquitoes. The experimental plan leverages the power of a comparison between natural mosquito populations that exhibit a striking difference in olfactory preference. An ancestral, forest form of the Dengue Fever Mosquito prefers the odor of non-human animals, while a recently evolved, domestic form strongly prefers human odor. The first (mentored) part of the project will compare the antennal, maxillary palp, and brain transcriptomes of these two forms to generate a list of candidate genes that may regulate preference. The second (mentored) part of the project will compare odor-evoked neurophysiological activity in the first processing center of the brain to pinpoint differences in host odor representation and generate hypotheses about how the candidates act through olfactory signaling cascades to alter behavior. The third (independent) part of the project will use a combination of functional and transgenic studies to test the specific hypothesis that changes in the sequence and/or pattern of expression of candidate chemoreceptors and other olfactory genes are essential for human host preference. The results are expected to provide insight into the way olfactory preferences are determined and will focus efforts to develop novel approaches to prevent mosquitoes from biting humans and transmitting human disease. PUBLIC HEALTH RELEVANCE: A keen sense of smell helps insects find and spread disease to hundreds of millions of people each year. The most deadly insect vectors of human disease are preferentially attracted to human scent over that of other animals. This project is designed to reveal the molecular basis of mosquito olfactory preference for human scent and could be useful for developing new ways to prevent insects from biting humans.