Acquistion of Equipment for Genomic Analysis Using Microarray Technology

06/19/98 微阵列技术的一个主要应用是基因表达模式的定量监测。 微阵列实验已经描述了最近，其中几十个新的差异表达的基因已被发现，使用显微组织和放射性标记和检测方法。 荧光检测方法提供了韧皮部定量，允许用不同荧光标记的两个样品与相同的微阵列网格共杂交，并且允许非常紧密间隔的微阵列斑点的分辨率。 然而，它确实具有增加费用的缺点，并且需要比放射性检测方法高得多的量的起始材料。 该提案将支持为使用微阵列技术进行基因组分析的最先进设施购买仪器。 将购买两种仪器：共聚焦激光扫描和成像装置，用于阅读与荧光标记的探针杂交的高密度微阵列，以及磷光成像仪，用于高分辨率扫描与放射性同位素标记的探针杂交的微阵列。 该技术支持的研究包括将微阵列分析与工程化转录抑制因子相结合以鉴定靶基因，酵母转录调控的基础研究，涉及转化和凋亡的细胞途径的研究，阐明亚核细胞学结构的生物学功能的新方法，小鼠组织再生和T细胞发育的研究，人类亚端粒变异和转录模式的分析，以及新型肽-核酸检测策略的开发。 Wistar研究所的研究生和博士后将有机会使用这项新兴技术，使他们能够在开发过程中将这种强大的新方法纳入他们的研究项目。 更重要的是，他们将看到令人兴奋的新机会微阵列分析提供了了解基本的生物过程，并将开始开发新的方法来解决生物学问题，可能已被视为困难或无法解决的使用非全球性的方法。

06/19/98 A major application of microarray technology is quantitative monitoring of gene expression patterns. Microarray experiments have been described recently in which dozens of new differentially expressed genes have been discovered using microdissected tissues and radioactive labeling and detection methods. Fluorescent detection methods afford the bast quantitation, permit co-hybridization of two samples labeled with different fluors to the same microarray grid, and permits resolution of very closely spaced microarrayed spots. However, it does have the drawback of increased expense and requires a much higher amount of starting material than radioactive detection methods. This proposal will support the purchase of instrumentation for a state-of-the-art facility that will use microarray technology for genomic analyses. Two instruments will be purchased: a confocal laser-scanning and imaging devise for reading high-density microarrays hybridized with probes labeled with fluorescent tags and a phosphoimager for high- resolution scanning of microarrays hybridized with probes labeled with radioisotopes. The research to be supported by this technology include combining microarray analysis with engineered transcriptional repressors for identification of target genes, fundamental studies of transcription regulation in yeast, studies of cellular pathways involved in transformation and apoptosis, novel approaches to elucidate the biological function of subnuclear cytological structures, studies of tissue regeneration and T-cell development in mice, analysis of subtelomeric variation and transcription patterns in humans, and the development of novel peptide-nucleic acid detection strategies. Graduate students and postdoctoral associates at the Wistar Institute will have access to this emerging technology, allowing them to incorporate this powerful new methodology into their research projects as they develop. More importantly, they will see the exciting new opportunities microarray analysis offers for understanding basic biological processes, and will begin to develop fresh approaches to biological problems that may have been seen as difficult or insoluble using non-global approaches.