Cytochrome P450 G subfamily member as a putativeodor

雌性蚊子是人类一些最令人衰弱的传染病的媒介。 目前的化学管理策略使用的杀虫剂几乎针对神经内分泌系统 独家。随着杀虫剂耐药性的上升，蚊媒疾病严重卷土重来， 因此，迫切需要为新战略制定新的目标。 大多数蚊子种类的雌性蚊子需要脊椎动物的血液来为产卵和 因此需要主要通过它们的嗅觉来定位合适的宿主。因此，蚊子 已经进化出一种敏锐的嗅觉信息处理系统，它可以检测和处理气味信息 启用气味源定位，最后快速停用气味信号，以保持高气味 敏感度。在过去的几十年里，研究极大地提高了我们对气味是如何 通过嗅觉回路检测和处理，气味信号失活的神经科学基础很差 明白了。 最近的研究表明，触角细胞色素P450(Cyps)在气味中起着重要作用 分子崩溃。在蜜蜂中，已经发现了昆虫特有的细胞色素P4G11亚家族成员 降解短链醇和醛(动植物气味中常见的挥发性气味分子)。 黄热病蚊子埃及伊蚊有两个具有功能的CYP4G同源基因，即CYP4G35和CYP4G36。 我们的初步数据显示，在头部和外周嗅觉组织中，CYP4G35的mRNA水平最高 (触角、上颌触须、鼻子和头部)。通过RNAi敲除CYP4G35导致脊椎动物宿主 成年人的回避。根据文献中的证据和我们的初步数据，我们假设 CYP4G35是一种气味降解酶，对气味清除很重要。我们将对此进行测试 通过两个特定目的的假说：目的1)评估CYP4G35基因敲除对寄主和配偶的影响 发现(嗅觉和交配)，并目的2)作为气味降解酶的CYP4G35的功能测定 通过确定酶的底物和在触角中的定位。我们将利用分子科学的技术 生物学、生物化学和神经科学/行为学来实现这些目标。 这项工作将通过提供1)蚊子控制的新目标和2)增强的目标来影响该领域 对蚊子嗅觉信息处理的理解。

Female mosquitoes are vectors for some of the most debilitating infectious diseases of humans. Current chemical management strategies use insecticides that target the neuro-endocrine system almost exclusively. With insecticide resistance on the rise, there is a serious resurgence of mosquito-borne diseases, and therefore an urgent need to develop new targets for new strategies. Female of most mosquito species require vertebrate blood to provide nutrients for egg production and therefore need to locate an appropriate host mainly through their sense of smell. Consequently, mosquitoes have evolved an acute olfactory information processing system that detects and processes odor information to enable localizing the odor source, and finally rapidly inactivates the odor signal so as to maintain high odor sensitivity. Studies in the last several decades have greatly improved our understanding of how odors are detected and processed by the olfactory circuit, the neuroscience underlying odor-signal inactivation is poorly understood. Recent studies have suggested that antennal cytochrome P450s (CYPs) play an important role in odor molecule breakdown. In honeybees, a member of insect-specific CYP subfamily, CYP4G11, has been shown to degrade short-chain alcohols and aldehydes (common volatile odor molecules in plants and animal odor). The yellow fever mosquito, Aedes aegypti, has two functional CYP4G orthologs, CYP4G35 and CYP4G36. Our preliminary data show that CYP4G35 mRNA levels are highest in the head and peripheral olfactory tissues (antennae, maxillary palps, proboscis, and head). CYP4G35 knockdown by RNAi results in vertebrate host avoidance by the adults. Based on the evidence in the literature and our preliminary data, we hypothesize that the CYP4G35 is an odor degrading enzyme, important for odor clearance. We will test this hypothesis through two specific aims: Aim 1) assessing the effects of CYP4G35 knockout on host and mate finding (olfaction and mating), and Aim 2) Functional determination of CYP4G35 as an odor degrading enzyme by determining enzyme substrates and localization in the antennae. We will employ techniques in molecular biology, biochemistry, and neuroscience/behavior to achieve these aims. This work will impact the field by providing 1) a novel target for mosquito control, and 2) an enhanced understanding of the olfactory information processing in mosquitoes.