CELL BIOLOGY AND PHYSIOLOGY OF GUSTATORY TRANSDUCTION

尽管人们对视觉和嗅觉的分子基础了解很多， 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道形式，甜、酸、苦和咸。 这项资助的重点是味觉的分子遗传解剖。 果蝇，一种特别适合于 在活体内对这一过程的遗传解剖。结果是意料之中的 从这些研究中获得的信息将对阐明 味觉的分子基础，将有助于我们对感官的理解 总体来说，这是一种信号。 我们将：(1)开发一种全面的基因筛查来分离突变 影响味觉细胞功能，包括甜、苦、咸 小路。(2)我们将筛查常染色体隐性突变，以便 生成广泛的基因数据库以进行详细分析和(3) 从遗传学和生理学角度描述突变体的特征。特别是， 我们将开发一种适用于生理分析和 将电生理记录与遗传上位性相结合 定位缺陷基因的作用部位。(4)我们将分离 并确定它们的整个核苷酸序列。野性 类型和突变拷贝将通过P-Element重新引入果蝇 介导的生殖系转化和拯救和/或测试 诱发味觉细胞功能障碍。我们将详细研究这些 基于它们的表达和遗传模式的序列 大多数生理指标都值得进一步研究。我们将定义 受影响基因座的正常功能，并确定分子 缺陷的基础。最后，(5)我们将利用果蝇的基因 分离相应的人类同源物，并制作这些序列 可供从事脊椎动物模型工作的社区使用。

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.