The Role of Odorant Binding Proteins in Anopheline Mosquito Odor Perception

气味结合蛋白在按蚊气味感知中的作用

• 批准号: 7924106
• 负责人: MARIKA F WALTER
• 金额: $ 44.68万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7924106
• 关键词: Affect; Africa South of the Sahara; Amino Acids; Anopheles gambiae; Attenuated; Behavior; Behavioral; Behavioral Assay; Binding; Biochemistry; Biological Assay; Chemicals; Collection; Computer Simulation; Culicidae; Data; Detection; Development; Dimerization; Discipline; Event; Feeding behaviors; Female; Gene Expression; Genes; Genomics; Goals; Human; In Situ Hybridization; In Vitro; Incidence; Individual; Indoles; Insect Control; Insecta; Institution; Knowledge; Laboratories; Lead; Ligand Binding; Ligands; Location; Malaria; Measurable; Mediating; Methods; Modeling; Molecular; Molecular Biology; Mutagenesis; Mutate; Neurons; Odorant Receptors; Odors; Output; Parasites; Pattern; Perception; Physiological; Physiology; Process; Property; Protein Binding; Proteins; RNA Interference; Radiolabeled; Reporter; Reporting; Research Personnel; Role; Screening procedure; Smell Perception; Specificity; Stimulus; Supporting Cell; System; Techniques; Testing; Validation; Work; arm; base; design; high throughput screening; improved; in vivo; novel; odorant-binding protein; radiotracer; receptor; research study; response; skills; small molecule; tool; vector

The work proposed here will investigate the specificity of odorant recognition in the malaria mosquito Anopheles gambiae and correlate odor stimuli with quantifiable physiological and behavioral responses. This work will integrate complementary expertise in various relevant fields toward the common goal of thoroughly understanding the chemosensory system and chemosensory-mediated behavior of A. gambiae. Odor recognition specificity is very likely encoded in both odorant binding proteins (OBPs) and odorant receptors (ORs). Recent evidence suggests that odor recognition is a coordinated process that requires the combined specificities contributed by OBPs and ORs. OBPs are the first proteins of the olfactory system to encounter odor molecules, and data from our and other laboratories demonstrate that OBPs are critical for the olfactory response in A. gambiae. This makes the odorant binding proteins a preferred target for manipulating odor perception. Thus, in vitro expressed OBPs will be used in high-throughput screening assays to identify natural ligands and deduce binding capacities for known and newly identified ligands. Computer modeling studies allow us to design mutagenesis-based experiments to define amino acids associated with the OBP binding pocket and predict modified ligands with improved properties. In vivo validation of all in vitro studies will be obtained through electrophysiological and behavioral assays employing female mosquitoes that express normal levels of OBPs or are deficient in a specific OBP as a result of RNAimediated gene expression knockdown. Knowledge gained from this multi-disciplinary approach will lead to the identification of chemicals that can interfere with host seeking behavior by female mosquitoes, reducing the incidence of contact between the human host and the parasite vector.

这里提出的工作将研究疟疾蚊子冈比亚按蚊气味识别的特异性，并将气味刺激与可量化的生理和行为反应相关联。这项工作将整合各个相关领域的互补专业知识，以实现彻底了解冈比亚的化学感应系统和化学感应介导的行为的共同目标。气味识别特异性很可能由气味结合蛋白（OBP）和气味受体（OR）编码。最近的证据表明，气味识别是一个协调的过程，需要 OBP 和 OR 贡献的组合特异性。 OBP 是嗅觉系统中第一个遇到气味分子的蛋白质，我们和其他实验室的数据表明，OBP 对于冈比亚疟原虫的嗅觉反应至关重要。这使得气味结合蛋白成为操纵气味感知的优选靶标。因此，体外表达的 OBP 将用于高通量筛选测定，以鉴定天然配体并推断已知和新鉴定的配体的结合能力。计算机建模研究使我们能够设计基于诱变的实验来定义与 OBP 结合袋相关的氨基酸并预测具有改进特性的修饰配体。所有体外研究的体内验证将通过使用表达正常水平 OBP 或由于 RNAi 介导的基因表达敲低而缺乏特定 OBP 的雌性蚊子进行电生理学和行为测定来获得。从这种多学科方法中获得的知识将导致识别出可以干扰雌性蚊子寻找宿主行为的化学物质，从而减少人类宿主与寄生虫媒介之间的接触发生率。

项目成果

The Anopheles gambiae odorant binding protein 1 (AgamOBP1) mediates indole recognition in the antennae of female mosquitoes.

• DOI: 10.1371/journal.pone.0009471
• 发表时间: 2010-03-01
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Biessmann H;Andronopoulou E;Biessmann MR;Douris V;Dimitratos SD;Eliopoulos E;Guerin PM;Iatrou K;Justice RW;Kröber T;Marinotti O;Tsitoura P;Woods DF;Walter MF
• 通讯作者: Walter MF

Mapping the Anopheles gambiae odorant binding protein 1 (AgamOBP1) using modeling techniques, site directed mutagenesis, circular dichroism and ligand binding assays.

• DOI: 10.1016/j.bbapap.2012.04.011
• 发表时间: 2012-08
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
• 影响因子: 3.2
• 作者: Rusconi, B.;Maranhao, A. C.;Fuhrer, J. P.;Krotee, P.;Choi, S. H.;Grun, F.;Thireou, T.;Dimitratos, S. D.;Woods, D. F.;Marinotti, O.;Walter, M. F.;Eliopoulos, E.
• 通讯作者: Eliopoulos, E.