权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Towards molecular mechanisms of invertebrate Gustatory Receptors

无脊椎动物味觉受体的分子机制

基本信息

批准号：
10064623
负责人：
RACHELLE GAUDET
金额：
$ 19.82万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10064623
关键词：
Behavior Binding Biochemical Biochemistry Blood Buffers Carbon Cells Chemicals Collaborations Complex Cryoelectron Microscopy Crystallography Cues Culicidae Data Dengue Diet Disease Disease Vectors Drosophila melanogaster Family Family member Fructose Future Goals Homo Human Insecta Invertebrates Ion Channel Gating Ligands Malaria Membrane Membrane Proteins Modality Molecular Nramp protein Nutrient Orthologous Gene Physiological Play Positioning Attribute Preparation Property Proteins Protocols documentation Research Personnel Role Sensory Sensory Receptors Sequence Analysis Smell Perception Stimulus Structure System Taste Perception Testing Ticks Variant West Nile virus Work ZIKA chikungunya comparative disorder control extreme temperature feeding fly human disease insect disease vector member olfactory receptor receptor receptor function receptor structure function sensor success sugar vector control

项目摘要

PROJECT SUMMARY Invertebrate Gustatory Receptors (GRs) are a large and evolutionarily diverse family of sensory receptors known to play important roles in invertebrate taste, smell and thermotransduction. Given the importance of these sensory modalities in host-seeking behavior in important humand disease vectors like mosquitoes, GR family members serve as potentially powerful targets for vector control agents. However, little is known about GR structure and function. We propose a physiological and biochemical analysis of members of two GR subfamilies: Gr43a and Gr28bD. These initial studies will serve as a precursor for a subsequent R01 to carry out structural and functional analyses of these GRs. We propose to achieve these goals in two aims: Aim #1: Identify and physiologically characterize multiple orthologs of Gr43a and Gr28bD. Unlike most GRs, Gr43a and Gr28bD orthologs can be functionally characterized in heterologous cells. In aim 1.a., we will express orthologs of these GRs from additional insect species, including disease vectors and extremophiles, in heterologous cells and characterize their physiological properties. This will enable a comparative analysis of sequence and function among each receptor class. Aim #2: Biochemically characterize multiple Gr43a and Gr28bD orthologs. We find Gr43a and Gr28bD orthologs can be partially purified from heterologous cells. In aim 2, we will expand this approach to incorporate additional orthologs characterized in aim 1 and optimize our purification protocol and explore key properties including oligomeric state and thermal stability in various membrane mimics. This will provide important biochemical information about GR complexes and identify orthologs best suited for subsequent structural analysis. The physiological characterization of multiple Gr43a and Gr28bD orthologs will enable direct examination of evolutionary variation and conservation in GR family function. The expression and purification of multiple family members will provide multiple candidates for biochemistry and structural determination, maximizing the likelihood of success of subsequent GR structural determinations.

项目总结