The Molecular Biology of Taste

味觉的分子生物学

• 批准号: 6401086
• 负责人: CHARLES S ZUKER
• 金额: $ 33.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6401086
• 关键词: biological signal transduction; chemoreceptors; complementary DNA; expression cloning; gene expression; gene targeting; genetic disorder; genetic markers; genetic screening; genetically modified animals; immunological substance; in situ hybridization; laboratory mouse; laboratory rabbit; molecular biology; mutant; protein structure function; protein transport; receptor; sensory feedback; taste; taste disorders; technology /technique development

The sense of taste is a major form of chemosensory input in the animal kingdom. Taste perception is responsible not only for attraction and repulsion to various food sources, but also for providing important information about the chemical environment. Our long-term goal is to define the components required for orchestrating the response of a taste receptor cell to its cognate ligands, and to help elucidate the logic of taste coding. This grant focuses on the identification of taste signaling molecules. We will: (1) Generate single cell libraries, perform differential screens and use subtraction approaches to identify genes expressed in subsets of taste receptor cells. These studies will use genetically marked cells isolated from mice expressing fluorescent reporters in defined subsets of taste receptor cells. (2) Develop heterologous expression system to (a) assay taste receptor function, and (b) to functionally clone novel receptors and downstream signaling molecules. We will also isolate and characterize "accessory" proteins required for receptor trafficking and maturation. Finally, (3) we will attempt to identify the genes responsible for taste defects in the sac, soa, rua and qui mutant strains.

在动物界，味觉是化学感觉输入的一种主要形式。味觉不仅负责对各种食物来源的吸引和排斥，还负责提供有关化学环境的重要信息。我们的长期目标是定义味觉受体细胞对其同源配体的反应所需的成分，并帮助阐明味觉编码的逻辑。这项拨款的重点是味觉信号分子的鉴定。我们将：(1)建立单细胞库，进行差异筛选，并使用差减方法来鉴定味觉受体细胞亚群中表达的基因。这些研究将使用从小鼠身上分离出来的基因标记细胞，在确定的味觉受体细胞亚群中表达荧光报告。(2)建立异源表达系统，以(A)检测味觉受体的功能，(B)从功能上克隆新的受体和下游信号分子。我们还将分离和鉴定受体运输和成熟所需的“辅助”蛋白。最后，(3)我们将尝试在sac、soa、rua和qui突变菌株中找出导致味道缺陷的基因。