Genetic Analysis of Mosquito Olfactory Preference for Humans

描述(申请人提供)：这个项目的目标是了解登革热蚊子对人类气味的强烈偏好背后的遗传机制。这项拟议的研究承诺(1)提供对嗅觉行为的分子基础的洞察，(2)提供有助于防止蚊子传播人类疾病的具体信息。这项实验计划利用了在嗅觉偏好方面表现出显著差异的自然蚊子种群之间的比较。一种原始的森林登革热蚊子更喜欢非人类动物的气味，而最近进化出来的一种家养蚊子更喜欢人类的气味。该项目的第一部分(被指导)将比较这两种形式的触角、上颌骨触须和大脑转录本，以生成可能调节偏好的候选基因清单。该项目的第二部分(有指导)将比较大脑第一处理中心气味引起的神经生理活动，以确定宿主气味表征的差异，并产生关于候选人如何通过嗅觉信号级联来改变行为的假设。该项目的第三部分(独立)将使用功能和转基因研究相结合的方法来测试特定的假设，即候选化学受体和其他嗅觉基因表达序列和/或模式的变化对人类宿主偏好至关重要。这些结果有望为确定嗅觉偏好的方式提供洞察力，并将集中精力开发防止蚊子叮咬人类和传播人类疾病的新方法。

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.