Biotechnology Center for Comparative Genomics

NIDDK生物技术中心的申请代表了华盛顿大学几个强大的研究社区的自然融合。这项提议将罗杰·布姆加纳博士领导下已经建立的i基因微阵列设施与研究人员结合在一起，研究领域包括糖尿病及其并发症的启动、免疫反应的控制、肾损伤中细胞增殖、细胞肥大和细胞迁移的调节、损伤后肝细胞再生、肠道发育和造血干细胞生物学。该中心的首要目标是开发一种工作基因芯片，其中包含所有已知的小鼠基因组序列验证基因，可供上述领域的研究人员使用。我们预计，这种方法将特别有利于研究人员利用海洋系统在纯化的细胞群体或特定器官系统中携带转基因、基因缺失或可控的基因突变来研究疾病的机制。我们同时寻求开发严格的数据生成和分析方法，以增加数量并建立信息的有效性，这些信息将作为将基因阵列方法应用于我们的疾病模型的结果而获得。这将通过以下四个具体目标来实现：1)通过获取Unigene组小鼠cDNA克隆和额外的人cDNA克隆，扩大可用于构建阵列的克隆的集合；2)提高阵列设施的吞吐量和数据存储容量；3)实施我们的数据分析并将其与表达数据库整合；4)测试和实施RNA和信号放大协议。

This application for an NIDDK Biotechnology Center represents a natural confluence of several strong research communities at the University of Washington. This proposal brings together an already established I gene microarray facility under the direction of Dr. Roger Bumgarner, with investigators at the cutting edge of research in the areas of initiation of diabetes and its complications, control of the immune response, regulation of cell proliferation, cell hypertrophy, and cell migration in renal injury, hepatocyte regeneration after injury, intestinal development, and hematopoietic stem cell biology. An overriding aim of this center is to develop a working gene chip containing all of the known sequence verified genes of the mouse genome, which can be utilized by investigators in the above areas. We anticipate this approach will particularly benefit investigators utilizing marine systems bearing transgenes, genetic deletions, or controllable genetic mutations in purified cell populations or specific organ systems to study mechanisms of disease. We concurrently seek to develop stringent approaches to data generation and analysis that will increase the amount and establish the validity of the information that will be obtained as the result of application of gene array approaches to our disease models. This will be accomplished through the following four specific aims: 1 ) Expand the collection of clones available for construction of arrays by acquiring Unigene sets of mouse cDNA clones and additional human cDNA clones; 2) Increase the throughput and data storage capacity of the array facility; 3) Implement and integrate our data analysis with an expression database; 4) Test and implement protocols for RNA and signal amplification.