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载体。特别地，嗅觉在吸血雌性蚊子的宿主寻找和选择行为中起主要作用，并且因此构成蚊子传播疾病如疟疾、登革热、黄热病和西尼罗河病毒脑炎的能力的关键组成部分。在这种情况下，我已经进行了几个元素的嗅觉信号转导级联的主要非洲疟疾媒介蚊子冈比亚按蚊狭义，在那里一个显着的偏好人类宿主（寄生虫）的基础上，其固有的能力，传播人类疟疾的分子检查。对嗅觉机制及其在该系统中的潜在化学线索的更多理解可以提供对一般昆虫行为反应过程和特别是媒介疾病传播过程的洞察。此外，这项研究可能有助于制定针对这一广泛的病媒家族以及其他昆虫的新的蚊子控制战略，这些昆虫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。该提案的目的是补充实验室正在进行的关于冈比亚按蚊嗅觉抑制蛋白的研究，并重点研究冈比亚按蚊中的一个候选气味受体蛋白家族。gambiae（AgORs）是本实验室最近发现的。到目前为止，我们已经确定了44个候选的AgOR，并进行了初步的表征，这个基因家族的一个小的子集。虽然在A.冈比亚，我们建议开始系统分析该基因家族，完成几项研究，重点是它们在蚊子中的表达。最初，为了建立一个战略计划，为未来的研究，我们将采用各种分子方法来确定AgOR家族成员，abrubt性别特异性表达模式。这些AgOR将形成我们的主要焦点组，用于随后表征AgOR的发育、空间和时间表达模式。此外，在扩展的初步研究，专门针对AgOR的嗅觉过程中的作用，疾病传播的基础，我们将建议进行一系列详细的实验，以检查AgOR表达的时间动力学，以响应血液喂养。

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.