The role of insect sweet taste receptors in detecting sweet and bitter compounds

昆虫甜味受体在检测甜味和苦味化合物中的作用

• 批准号: 8684997
• 负责人: Erica Freeman
• 金额: $ 3.88万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8684997
• 关键词: Achievement; Address; Aedes; Alkaloids; Animal Model; Anopheles gambiae; Area; Arthropods; Award; Biological; Biomedical Engineering; Categories; Centers for Disease Control and Prevention (U.S.); Chemicals; Chemoreceptors; Complex; Culicidae; Detection; Disease; Disease Vectors; Drosophila genus; Drosophila gustatory receptor; Drosophila melanogaster; Ectopic Expression; Engineering; Family; Family member; Female; Food; Foundations; Genetic; Goals; Individual; Insect Control; Insecta; Knowledge; Malaria; Methods; Modality; Modeling; Mosquito Control; Neurons; Odors; Partner in relationship; Population; Property; Receptor Gene; Reporting; Research; Research Personnel; Role; Source; Stimulus; Structure-Activity Relationship; System; Taste Perception; Testing; Toxin; Training; Trehalose; Work; design; experience; feeding; fly; genetic analysis; in vivo; innovation; interest; killings; male; neurophysiology; novel; prevent; public health relevance; receptor; receptor function; response; sensor; success; sugar; sweet receptor; sweet taste perception; tool

DESCRIPTION (provided by applicant): All insects, including mosquitoes, must be able to determine the palatability of potential food sources. This makes the use of sugar-baited traps an effective method to control the spread of mosquito borne illnesses. D. melanogaster is a model organism to study gustation because the fly can detect a broad range of compounds but has a relatively simple neurophysiology. Gustatory receptors (Gr) are expressed in taste neurons and members of this family are implicated in the detection of sweet or bitter tastants by genetic analyses. However, there has been little success in expressing these receptors in heterologous expression systems, which has led to a critical gap in understanding the functional properties of individual insect Grs, as well as in identifying the composition of a functional insect taste receptor. This represents an important problem because Grs belong to a family that is highly conserved in insects and non-insect arthropods. To address this problem, we will use two parallel approaches to study sweet taste receptors in Drosophila and mosquitoes, taking advantage of a novel in vivo expression system that we have designed for decoding Drosophila gustatory receptor proteins. Using this approach, I have identified sugar response profiles of each of the putative sweet taste receptors in D. melanogaster. Moreover, using recordings with mixed stimuli I have found that sweet taste receptors in Drosophila are directly inhibited by bitte alkaloids. This mechanism may be evolutionarily conserved since labellar sweet taste neurons in An. gambiae and Ae. aegypti are inhibited by alkaloids as well. The proposed project is innovative because this is the first report of successful expression of sweet taste receptors in a heterologous neuron in vivo. The hypothesis is that each receptor in both D. melanogaster and An. gambiae can individually respond to a unique set of sweet compounds and is inhibited by a distinct set of alkaloids. The rationale is that by understanding how insect taste receptors detect attractive and aversive compounds, we can then screen for novel compounds that can be used in insect control strategies. My objectives will be achieved via two specific aims: (1) Identify an characterize the functional properties of trehalose receptors in Drosophila, and (2) Identify and characterize the functional properties of select mosquito sweet taste receptors. This project will reveal the composition and response properties of a functional trehalose receptor. My studies will lay the foundation to probe structure-function relationships of sweet receptor's in Drosophila and An. gambiae in terms of detection of chemicals of both sweet and bitter categories with opposing effects on receptor activity. The significance of the proposed project is that it will advance our understanding of a highly conserved insect chemoreceptor family and establish a system to study insect gustatory receptor function by ectopic expression. The proposed project will enhance my training to be an independent researcher and allow me to use engineering principles to solve biological questions about sweet receptors. I will also gain experience in working with the disease vector An. gambiae.

描述（由申请人提供）：所有昆虫，包括蚊子，都必须能够确定潜在食物来源的可口性。这使得使用糖诱饵陷阱是控制蚊子传播疾病传播的有效方法。 D. melanogaster是一种研究味的模型生物体，因为苍蝇可以检测到广泛的化合物，但具有相对简单的神经生理学。味觉受体（GR）在味觉神经元中表达，该家族的成员与通过遗传分析一起检测甜或苦味的味道剂。但是，在异源表达系统中表达这些受体几乎没有成功，这导致了了解单个昆虫GRS的功能性能以及鉴定功能性昆虫味道受体的组成的危险差距。这代表了一个重要的问题，因为GRS属于在昆虫和非侵蚀性节肢动物中高度保守的家族。为了解决这个问题，我们将使用两种平行方法来研究果蝇和蚊子中的甜味受体，利用一种新型的体内表达系统，我们设计了用于解码果蝇阵风受体蛋白。使用这种方法，我确定了D. melanogaster中每个假定的甜味受体的糖反应曲线。此外，使用混合刺激的录音，我发现果蝇中的甜味受体直接被Bitte生物碱抑制。这种机制在进化上可能是保守的，因为在An中的Labellar甜味神经元。冈比亚和AE。埃及也被生物碱抑制。拟议的项目具有创新性，因为这是在体内的异源神经元中成功表达甜味受体的第一个报道。假设是D. melanogaster和An中的每个受体。冈比亚可以单独反应一组独特的甜化合物，并被一组不同的生物碱抑制。理由是通过了解昆虫味道受体如何检测 然后，我们可以筛选有吸引力和厌恶的化合物，以筛选可用于昆虫控制策略的新型化合物。我的目标将通过两个特定的目的来实现：（1）确定果蝇中海藻糖受体的功能特性的特征，（2）识别和表征选择蚊子甜味受体的功能特性。该项目将揭示功能性海藻糖受体的组成和响应特性。我的研究将奠定基础，以探测果蝇中甜受体的结构功能关系 和一个。冈比亚在发现对受体活性影响的甜和苦味类别的化学物质方面。拟议项目的意义在于，它将提高我们对高度保守的昆虫化学感受器家族的理解，并建立通过异位表达研究昆虫味道受体功能的系统。拟议的项目将增强我的培训，成为一名独立的研究人员，并允许我使用工程原理来解决有关甜蜜受体的生物学问题。我还将获得与疾病媒介AN合作的经验。冈比亚。