Examination of Odorant Receptors in Anopheles gambiae

描述（由申请人提供）：化学感觉反应是指导昆虫几种基本行为的关键组成部分，昆虫是导致许多重要人类疾病的病原体的媒介。特别是，嗅觉在吸血雌蚊寻找宿主和选择行为中起着重要作用，因此是蚊子传播疟疾、登革热、黄热病和西尼罗河尼罗病毒脑炎等疾病的能力的关键组成部分。在此背景下，我对非洲主要疟疾媒介冈比亚按蚊（Anopheles gambiae sensustricto）嗅觉信号转导级联的几个要素进行了分子检查，其中对人类宿主的显著偏好（亲人类）是其传播人类疟疾的内在能力的基础。对嗅觉机制及其在这一系统中潜在的化学线索的进一步了解，可能为了解昆虫行为反应的一般过程，特别是病媒疾病的传播过程提供洞见。此外，这项研究可能有助于制定新的蚊子控制策略，针对这一广泛的病媒家族，以及其他通过传播疾病和作为农业害虫的能力构成相当大的医疗和经济威胁的昆虫。本提案的目标是补充实验室正在进行的冈比亚冈比亚嗅觉阻滞研究，并重点研究该实验室最近发现的冈比亚冈比亚冈比亚嗅觉受体候选蛋白家族（AgORs）。到目前为止，我们已经确定了44个候选AgORs，并对该基因家族的一小部分进行了初步表征。虽然冈比亚疟蚊中潜在AgORs的确切数量仍有待确定，但我们建议通过完成几项研究，重点研究它们在冈比亚疟蚊中的表达，开始对该基因家族进行系统分析。首先，为了建立未来研究的战略计划，我们将采用多种分子方法来鉴定表现出性别特异性表达模式的AgOR家族成员。这些AgORs将成为我们随后表征AgORs的发育、空间和时间表达模式的主要焦点群体。此外，在初步研究的延伸中，专门针对AgOR在疾病传播基础嗅觉过程中的作用，我们将建议进行一系列详细的实验，以检查AgOR在血液喂养反应中的表达的时间动力学。

DESCRIPTION (provided by applicant): Chemosensory responses are critical components that direct several essential 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 and as such constitutes a critical component of the mosquito's ability to transmit diseases such as malaria, dengue, yellow fever and West Nile Nile virus encephalitis. Within this context, I have undertaken a molecular examination of several elements of the olfactory signal transduction cascade in the principal African malaria vector mosquito Anopheles gambiae sensu stricto, where a significant preference for human hosts (anthropophily) underlies its inherent ability to transmit human malaria. An increased understanding of olfactory mechanisms and their underlying chemical cues in this system may provide insight in the processes of insect behavioral responses in general and vector disease transmission in particular. Moreover, this study would likely be instrumental in the development of novel mosquito control strategies targeted against this broad family of disease vectors, as well as other insects that pose considerable medical and economic threats through their ability to transmit disease and to act as agricultural pests. The objectives of this proposal complements ongoing studies in the laboratory of olfactory arrestins in A.gambiae and focus on an examination of a family of candidate odorant receptor proteins in A. gambiae (AgORs) that has recently been identified by this laboratory. Thus far, we have identified 44 candidate AgORs and have performed an initial characterization of a small subset of this gene family. While the exact number of potential AgORs remain to be established in A. gambiae, we proposed to begin a systematic analysis of this gene family by completing several studies focusing on their expression in the mosquito. Initially, in order to establish a strategic plan for future studies, we will employ a variety of molecular approaches to identify AgOR family members that exhibt sex-specific expression patterns. These AgORs will form our primary focus group for subsequent characterization of the developmental, spatial and temporal expression pattems of AgORs. In addition, in an extension of initial studies that specifically targets AgOR's role in the olfactory processes that underlie disease transmission, will we propose to conduct a series of detailed experiments to examine the temporal kinetics of AgOR expression in response to blood feeding.