Functional Domains and Expression of Olfactory Receptors

描述（由申请人提供）：哺乳动物嗅上皮的嗅觉感觉神经元有两个显著的功能。这些神经元检测气味，将挥发性化学物质的结构翻译成神经信息代码，即使这些神经元被完全消除，上皮也可以取代它们。这些特性对于基础和应用神经科学研究都具有重要意义。该项目的目标是生成成熟嗅觉感觉神经元及其直接祖细胞的表型的精细详细描述，然后使用此描述来预测导致这些神经元发生的分子机制中的关键步骤，它们检测某些气味的能力，以及它们在暴露位置生存的能力。该项目的第一个目标是将基因表达的全系统观点与我们纯化某些细胞类型的能力相结合，以便我们可以将基因表达模式和它们所代表的生物过程分配给上皮细胞中的正确家园。第二个目标利用了我们的初步数据对基因的预测，这些基因的产物调节其他基因的活性。我们将测试是否有针对性地敲除这些调节基因中的六个，所有这些基因都由不成熟的嗅觉感觉神经元表达，导致成熟神经元的产生或这些神经元的关键功能的缺陷。第三个目标是基于我们的信念，即我们在嗅觉感觉神经元中观察到的表达模式是负责神经元存活的基因组。我们将使用气味刺激，这是众所周知的，以提高生存，以增加促生存基因的活性（或抑制抗生存基因），使他们可以被检测到。该项目是一个综合的方法来了解基因的活性是重要的成熟嗅觉感觉神经元的表型产生，然后保持这些细胞在面对重大挑战。

DESCRIPTION (provided by applicant): The mammalian olfactory epithelium does two remarkable things with its olfactory sensory neurons. These neurons detect odorants, translating the structure of volatile chemicals into a neural information code, and the epithelium can replace these neurons even if they are completely eliminated. These properties are of significant interest for both basic and applied neuroscience research. The goal of this project is to generate a finely detailed description of the phenotypes of the mature olfactory sensory neurons and their immediate progenitor cells, then use this description to predict critical steps in the molecular mechanisms that lead to the genesis of these neurons, their ability to detect certain odors, and their ability to survive in their exposed position. The first aim of this project combines a system-wide view of gene expression with our ability to purify certain cell types so that we can assign gene expression patterns and the biological processes they represent to their correct homes in the cells of the epithelium. The second aim takes advantage of predictions about genes whose products regulate the activity of other genes made by our preliminary data. We will test whether targeted knockout of six of these regulator genes, all expressed by immature olfactory sensory neurons, causes deficits in either the production of mature neurons or in critical functions of these neurons. The third aim is based on our belief that within the expression patterns we observe in olfactory sensory neurons are sets of genes responsible for survival of the neurons. We will use odor stimulation, which is known to enhance survival, to increase the activity of pro-survival genes (or suppress anti-survival genes) so that they can be detected. This project is an integrated approach to understanding the genes whose activity is important for generating the phenotype of mature olfactory sensory neurons and then maintaining these cells in the face of significant challenges.