Analysis of Chemosensory Receptor Genes

描述（由申请人提供）：该项目的长期目标是解释化学信号编码的逻辑，并阐明编码这些信号的神经元的组织和发育的基本原理。本实验计划以果蝇黑腹果蝇为模型系统，对化学感觉基因进行深入的分子遗传学分析，对化学感觉功能进行生理和行为分析。该项目研究了一个由30个预测的化学受体基因组成的新家族，IR20a家族，其表达和功能完全未知。第一个目标是将这些基因映射到成年果蝇化学感觉器官的神经元上，并检查它们在中枢神经系统中的投射。其目的是解决感觉生物学中的一个主要问题：一个感觉系统如何整合多种输入，最终转化为行为反应。这一目标的一个可能结果是，它将支持IR20a家族作为无脊椎动物味觉受体的主要新家族的身份。第二个目标是在幼虫阶段绘制受体到神经元的图谱。这些受体彼此之间以及与其他类型的化学受体的共表达将被分析。它们的发育特征和在神经元中表达的细胞位置将被确定。这一目标有望支持这些受体作为幼虫味觉受体的主要新家族的身份。第三个目的是直接测试这些受体的功能。关于化学接受和神经元发育中的作用的假设将通过生理和行为测量以及神经元形态和投射的检查进行测试。将测试它们在喂养调节中发挥双重作用的模型。饲养调节的分子和细胞基础对公众健康具有重大影响。昆虫携带的疾病每年折磨着数亿人，其中许多昆虫通过化学感觉线索找到它们的人类宿主和配偶。对化学感觉接受的理解的进展可能会导致控制这些人类疾病的昆虫媒介的新方法。

DESCRIPTION (provided by applicant): The long-term goal of this project is to explain the logic by which chemical signals 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 chemosensory genes as well as physiological and behavioral analysis of chemosensory function. The project investigates a new family of 30 predicted chemoreceptor genes, the IR20a family, whose expression and function are completely unexplored. The first aim is to map these genes to neurons of chemosensory organs in the adult fly, and to examine their projections in the central nervous system. The aim is designed to address a major problem in sensory biology: how a sensory system integrates the multiple inputs that are ultimately translated into a behavioral response. A likely outcome of this aim is that it will support the identity of the IR20a family as a major new family of invertebrate taste receptors. The second aim is to produce a receptor-to-neuron map in the larval stage. The coexpression of these receptors with each other and with other classes of chemoreceptors will be analyzed. Their developmental profile and cellular location of expression in neurons will be determined. This aim is expected to support the identity of these receptors as a major new family of larval taste receptors. The third aim tests the function of these receptors directly. Hypotheses concerning roles in chemoreception and in neuronal development will be tested through physiological and behavioral measurements, and by examination of neuronal morphology and projections. A model in which they play a dual role in the regulation of feeding will be tested. The molecular and cellular basis of feeding regulation has major implications for public health. Diseases carried by insects afflict hundreds of millions of people each year, and many of these insects locate their human hosts and their mates through chemosensory cues. Advances in the understanding of chemosensory reception may lead to new means of controlling these insect vectors of human disease. 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 preventing insects from identifying humans. 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.