MOLECULAR GENETICS OF OLFACTION IN ANOPHELINE MOSQUITOES

描述（改编自申请人的摘要）：感知和感知的能力。 区分大量的化学和视觉线索是核心， 昆虫的几种行为是病原体的载体， 许多重要的人类疾病。尤其是嗅觉在 吸血雌蚊的寄主寻找和选择行为 （双翅目：蚊科），因此，构成了一个关键组成部分， 蚊子传播疟疾和登革热等疾病的能力。 此外，对人类宿主的强烈偏好（寄生性）表现为 主要的非洲疟疾媒介蚊子冈比亚按蚊形成 这在很大程度上是其固有的传播人类疟疾能力的基础。在 就像了解这些化学感受机制及其 潜在的化学线索可能有助于开发抗疟疾药物， 针对按蚊病媒介的控制策略， 这些蚊子的特征已经开始。 本研究的目的主要是研究 包括基因的分离和鉴定 组成了An的嗅觉器官的外围组件。 gambiae和An.四环带的我们假设这些基因编码 气味结合蛋白（OBP）、气味受体（ORs）和它们的 相应的逮捕更有可能是针对寻找宿主的 而不是下游，因此更多 广义的，信号转导级联的组成部分。初步 研究，已采取替代办法，以产生 来自雌性蚊子的嗅觉富集的cDNA库产生克隆 对于几类可能具有嗅觉作用的cDNA，包括推定的 从一个OBP和逮捕。冈比亚有限公司这项建议旨在扩大这些 分子筛与详细表征的发展，空间 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 嗅觉抑制蛋白的表征，特别强调 功能测定法，以鉴定蛋白质-蛋白质相互作用， 包括ORs在内的目标。为了进一步完善这一分析，比较 屏幕将在一个。冈比亚有限公司而且它是嗜动物的 非向量同胞An. quadriannulatus用于识别和表征外周 嗅觉基因，其与嗅觉和/或嗅觉相关， 嗜兽癖

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.