GENETIC ANALYSIS OF OLFACTION

该研究计划的广泛，长期的目标是确定果蝇化学感觉歧视所需的基本分子和细胞成分。 这种化学感受模型系统与脊椎动物化学感受系统有许多相似之处，但在数值上更简单。 果蝇中有效的分子遗传学工具与简单的化学感受行为分析相结合，将使我们能够深入了解化学感受信息处理的原理。 具体目标是：1. 鉴定、分离和确定化学感受器官中专门表达的基因产物的集合的生物学功能，2。 鉴定果蝇神经元跨膜气味受体，并描述单个成员的表达模式。区分气味结合蛋白影响化学感觉行为的几种可能的模型。 健康相关性：了解果蝇化学感受的分子基础将为了解传播人类疾病的相关节肢动物的这一过程提供见解。 这一认识将促进新的方法来控制这些疾病。 实现具体目标1的方法是利用增强子捕获方法来鉴定、分离、突变和确定我们已经鉴定的仅在化学感受器官中表达的基因集合的生物学功能。 这种方法使我们能够评估这些化学感觉特异性基因产物在完整动物中的生物学功能。 实现具体目标2的方法是使用差异杂交和单个化学感受神经元文库来鉴定神经元化学感受器。 我们将使用针对特定受体的抗体和受体基因的启动子来驱动LacZ报告基因，以绘制每个基因的空间表达模式。 识别介导化学感觉的神经元受体对于我们理解化学感觉辨别的分子基础的长期目标至关重要。用于实现目标3的方法是在感器的特定子集中错误表达具有已知配体特异性的气味结合蛋白家族的几个成员，以使化学感觉神经元的子集对特定气味敏感，并确定所产生的行为后果。

The broad, long-term objectives of the research program are to define the basic molecular and cellular components required for chemosensory discrimination in Drosophila. This chemosensory model system has many parallels with vertebrate chemosensory systems, but is numerically simpler. The potent molecular genetic tools available in Drosophila combined with simple chemosensory behavior assays will allow us to gain insight into the principles of chemosensory information processing. The specific aims are to: 1. Identify, isolate and determine the biological function of a collection of gene products expressed exclusively in the chemosensory organs, 2. Identify the neuronal transmembrane odorant receptors in Drosophila, and characterize the expression patterns of individual members, and 3. Differentiate between several possible models by which odorant- binding proteins influence chemosensory behavior. Health relatedness: Understanding the molecular basis of chemosensation in Drosophila will provide insights into this process in related arthropods that transmit human diseases. This understanding will faciliate new approaches to control these diseases. The methods for achieving specific aim 1 are to utilize the enhancer trapping approach to identify, isolate, mutate and determine the biological function of a collection of genes we have identified that are expressed exclusively in the chemosensory organs. This method allows us to evaluate the biological function of these chemosensory-specific gene products in intact animals. The methods for achieving specific aim 2 are to use differential hybridization and single chemosensory neuron libraries to identify neuronal chemoreceptors. We will use antibodies to specific receptors and the promoters of receptor genes to drive LacZ reporter genes to map the spatial expression patterns of each gene. Identification of the neuronal receptors that mediate chemosensation is essential to our long-range goal of understanding the molecular basis of chemosensory discrimination. The methods for achieving aim 3 are to mis-express several members of the odorant-binding protein family with known ligand specificity in specific subsets of sensilla to sensitize subsets of chemosensory neurons to specific odorants and determine the resulting behavioral consequences.