Analysis of a Large Family of Candidate Taste Receptors

描述（由申请人提供）：该项目的长期目标是揭示促味剂编码的逻辑，并阐明编码它们的神经元的组织和发育的基本原理。该实验计划利用果蝇Drosophila melanogaster作为模型系统，其允许对味觉基因进行精辟的分子遗传学分析以及对味觉功能进行生理学分析。第一个目标是完成一个数字上简单的模型味觉器官，前腿的功能分析。这个器官的味觉神经元已经被定义，并且味觉受体的Gr家族的所有成员都被映射到它们。该器官对糖，苦味化合物和氨基酸的生理反应将被分析，以了解该器官在味觉评价中的作用。该分析旨在解决感觉系统如何整合最终转化为行为反应的多个输入的问题。这些结果可能支持一个模型，解释动物如何做出对所有动物都至关重要的决定：是接受还是拒绝潜在的食物来源。饲养管理的基础对公共卫生有重大影响。第二个目标是解决G蛋白在味觉神经元信号传导和发育中的作用。这些蛋白质在化学感受信号中的作用是该领域的中心问题。该分析将测试这样的假设，即完全去除某些G蛋白会导致对糖或苦味化合物的生理反应完全丧失。这些蛋白质在味觉神经元的发育中起作用的假设也将被检验。第三个目标是通过在没有苦味反应的细胞中表达苦味受体来检查其功能。该分析旨在检验Gr家族的某些成员作为其他成员的共受体的假设。它还旨在确定是否可以构建一个有效的系统，用于研究苦味受体和识别激活或抑制它们的促味剂。这些结果可能为研究苦味受体的功能及其在苦味感知中的作用提供了大量新的机会。昆虫携带的疾病每年折磨数亿人，这些昆虫从人类宿主那里获得味觉线索。对味觉理解的进步可能会导致控制这些人类疾病昆虫载体的新方法。特别是，识别激活或抑制苦味受体的化合物可以为控制昆虫媒介及其传播的疾病提供新的药剂。 公共卫生相关性：昆虫每年将疾病传播给数亿人，许多疾病的昆虫媒介通过它们的化学感受系统识别人类。该项目旨在揭示昆虫化学感受的基本原理，并可能有助于开发控制携带疾病的昆虫的新方法。该项目还涉及决定是否接受或拒绝潜在食物来源的分子和细胞基础，这是由所有动物做出的，对公共卫生具有重要影响。

DESCRIPTION (provided by applicant): The long-term goal of this project is to reveal the logic by which tastants are encoded, and to elucidate basic principles of the organization and development of the neurons that encode them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis of taste genes as well as physiological analysis of taste function. The first aim is to complete a functional analysis of a numerically simple model taste organ, the foreleg. The taste neurons of this organ have been defined and all members of the Gr family of taste receptors have been mapped to them. Physiological responses of this organ to sugars, bitter compounds and amino acids will be analyzed with a view to understanding the role of this organ in the evaluation of taste. The analysis is designed to address the problem of how a sensory system integrates the multiple inputs that are ultimately translated into a behavioral response. The results may support a model explaining how the animal makes a decision critical to all animals: whether to accept or reject a potential food source. The underlying basis of feeding regulation has major implications for public health. The second aim addresses the role of G proteins in taste neuron signaling and development. The role of these proteins in chemosensory signaling is a central question in the field. The analysis will test the hypothesis that complete removal of certain G proteins leads to a complete loss of physiological response to either sugars or bitter compounds. The hypothesis that these proteins act in the development of taste neurons will also be tested. The third aim is to examine the function of a bitter receptor by expressing it in cells that have no bitter response. The analysis is designed to test the hypothesis the certain members of the Gr family act as co-receptors for other members. It is also designed to determine whether an efficient system can be constructed for the study of bitter receptors and for the identification of tastants that activate or inhibit them. The results could yield a wealth of new opportunities to study the function of bitter receptors and their role in the perception of bitter taste. Diseases carried by insects afflict hundreds of millions of people each year, and these insects receive taste cues from their human hosts. Advances in the understanding of taste may lead to new means of controlling these insect vectors of human disease. In particular, the identification of compounds that activate or inhibit bitter taste receptors could provide new agents for the control of insect vectors and the diseases they transmit. PUBLIC HEALTH RELEVANCE: Insects transmit disease to hundreds of millions of people each year, and many insect vectors of disease identify humans through their chemosensory systems. This project is designed to reveal basic principles of insect chemosensation and could be useful in developing new means of controlling insects that carry disease. The project also concerns the molecular and cellular basis of a decision, whether to accept or reject a potential food source, which is made by all animals and which has important implications for public health.