MOLECULAR GENETICS OF OLFACTION IN ANOPHELINE MOSQUITOES

描述(改编自申请者的摘要)：感知和 辨别大量的化学和视觉线索是 作为病原体媒介的昆虫的几种行为 许多重要的人类疾病。特别是，嗅觉在 食血雌蚊的寄主寻找和选择行为 (双翅目：蚊科)，因此，构成了 蚊子传播疟疾和登革热等疾病的能力。 此外，人类对宿主的强烈偏好(以人类的方式)表现出 非洲主要的疟疾媒介蚊子冈比亚按蚊。表格a 这在很大程度上是其传播人类疟疾的固有能力的基础。在……里面 就像了解这些化学传感机制和它们的 潜在的化学线索可能对开发抗疟疾药物有用 针对按蚊病媒的控制策略 已经开始对这些蚊子进行定性。 这项研究的目的是考察分子遗传学。 包括基因的分离和特征 它们构成了嗅觉器的外围部件。 冈比亚亚纲和An.四环龙。我们假设这些编码基因 气味结合蛋白、气味受体及其受体 相应的逮捕更有可能是针对寻找寄主的 此向量中的行为，而不是下游的行为，因此更多 广义的，信号转导级联的组成部分。在预赛中 研究表明，已经采取了替代办法，以产生 来自雌性蚊子的嗅觉丰富的cDNA池产生克隆 对于几类可能具有嗅觉作用的cdna，包括推测的 OBP和逮捕来自一个。冈比亚亚种这项提案旨在延长这些 分子筛具有详细的表征发展、空间 以及这些cDNA及其蛋白产物的时间表达模式 在蚊子的嗅觉器官里。此外，一种生物化学 嗅觉阻滞剂的特征，特别强调 用功能实验鉴定潜在的蛋白质相互作用 提出了包括ORs在内的目标。为了进一步完善这一分析，比较 放映工作将在两个月之间进行。冈比亚亚种而且它是嗜动物性的 非向量同级AN。四环肌用于识别和表征外周组织 嗅觉基因，与人类和/或 嗜动物性的。

DESCRIPTION (Adapted from the Applicant's Abstract): The ability to sense and discriminate a large collection of chemical and visual clues is central for several behaviors of insects that are vectors for pathogens responsible for many important human diseases. In particular, olfaction plays a major role in host seeking and selection behavior of blood-feeding female mosquitoes (Diptera: Culicidae) and as such, constitutes a critical component of the mosquito's ability to transmit diseases such as malaria and dengue. Furthermore, the strong preference for human hosts (anthropophily) exhibited by the principal African malaria vector mosquito Anopheles gambiae s.s. forms a large part of the basis for its inherent ability to transmit human malaria. In as much as an understanding of these chemosensory mechanisms and their underlying chemical cues may be useful in the development of anti-malarial control strategies targeted against Anopheline disease vectors, a molecular characterization in these mosquitoes has been initiated. The objectives of this study focus on an examination of the molecular genetics of anthropophily and consist of the isolation and characterization of genes that make up the peripheral components of the olfactory apparatus in An. gambiae and An. quadriannulatus. We hypothesize that these genes encoding odorant binding proteins (OBPs), odorant receptors (ORs) and their corresponding arrestins are more likely to be specific for host seeking behaviors in this vector rather than downstream, and therefore more generalized, components of the signal transduction cascade. In preliminary studies, alternative approaches have been undertaken to generate olfactory-enriched cDNA pools derived from female mosquitoes yielding clones for several classes of cDNA with possible olfactory roles including putative OBPs and arrestins from An. gambiae s.s. This proposal seeks to extend these molecular screens with a detailed characterization of the development, spatial and temporal expression patterns of these cDNAs and their protein products within the mosquito's olfactory apparatus. In addition, a biochemical characterization of olfactory arrestins with a particular emphasis on a functional assay to identify protein-protein interactions with potential targets including ORs is proposed. To further refine this analysis, comparative screens will be undertaken between An. gambiae s.s. and it's zoophilic non-vector sibling An. quadriannulatus to identify and characterize peripheral olfactory genes, which are specifically associated with anthropophily and/or zoophily.