CELL BIOLOGY AND PHYSIOLOGY OF GUSTATORY TRANSDUCTION

尽管我们对视觉和嗅觉的分子基础已经了解很多， 人们对味觉的分子生物学几乎一无所知。人类和 苍蝇有四种基本的味觉形态：甜、酸、苦和咸。 这项资助的重点是对味觉的分子遗传解剖， 黑腹果蝇，一个特别适合于 对这一过程进行基因解剖。预计结果 从这些研究中获得的信息将对阐明 味觉的分子基础，并将有助于我们理解感官 信号一般。 我们将：（1）开展全面的基因筛查，隔离突变 影响味觉细胞功能，包括甜、苦和咸 途径。(2)我们将筛查常染色体隐性突变， 生成用于详细分析的广泛的基因数据库，以及（3） 从基因和生理上描述突变体。特别是， 我们将开发一种适合于生理分析的制剂， 利用电生理记录和遗传上位性， 定位缺陷基因的作用位点(4)我们将隔离 缺陷基因并确定其整个核苷酸序列。野生 型和突变型拷贝将通过P-元件被引入果蝇体内 介导的生殖系转化，并测试其拯救和/或 诱导味觉细胞功能障碍。我们将详细研究 基于它们的表达模式和遗传和 生理标准最值得进一步研究。我们将定义 受影响的基因座的正常功能，并确定分子 缺陷的基础。最后，（5）我们将使用果蝇基因， 分离出相应的人类同源物， 提供给从事脊椎动物模型研究的社区。

Although much is known about the molecular basis of vision and olfaction, almost nothing is known about the molecular biology of taste. Humans and flies have four basic taste modalities, sweet, sour, bitter and salty. This grant focuses on a molecular genetic dissection of taste in Drosophila melanogaster, a model system particularly well suited for a genetic dissection of this process in vivo. It is expected that results obtained from these studies will be important in elucidating the molecular basis of taste, and will help our understanding of sensory signaling in general. We will: (1) Develop a comprehensive genetic screen to isolate mutations affecting taste cell function, including sweet, bitter and salty pathways. (2) We will screen for autosomal recessive mutations so as to generate an extensive genetic database for detailed analysis and (3) characterize the mutants genetically and physiologically. In particular, we will developed a preparation suitable for physiological analysis and use electrophysiological recording together with genetic epistasis to localize the site of action of the defective genes.(4) We will isolate the defective genes and determine their entire nucleotide sequence. Wild type and mutant copies will be introduced back into flies by P-element mediated germ line transformation and tested for rescuing and/or induction of taste cell dysfunction. We will study in detail those sequences which based on their patterns of expression and genetic and physiological criteria most warrant further investigation. We will define the normal function of the affected loci, and determine the molecular basis of the defect. Finally, (5) we will use the Drosophila genes to isolate the corresponding human homologs, and make those sequences available to the community working on vertebrate models.