DEVELOPMENT OF DNA MICROARRAYS RESOURCE FOR C ELEGANS

我们正在进入一个分子遗传学的新时代，在这个时代，我们可以利用基因组计划的序列数据，比以往任何时候都更全面、更灵敏地解剖细胞、发育和疾病途径。我们需要开发新的实验方法来分析目前从基因组计划中获得的大量数据。秀丽隐杆线虫是唯一具有完整基因组序列的动物模型系统，因此将在建立利用全基因组序列的方法方面发挥主导作用。一个关键的功能基因组学方法是使用DNA微阵列来确定发育和发病期间基因表达模式的变化。我们的目标是在斯坦福为蠕虫学术界建立一个中心来进行DNA微阵列实验。据我所知，我们的实验室是唯一一个拥有秀丽隐杆线虫DNA微阵列的实验室，因此我们是秀丽隐杆线虫学术界DNA微阵列的唯一潜在资源。我们将和我们的合作者一起计划DNA微阵列实验，然后用他们寄给我们的RNA样本进行DNA微阵列实验。我们正在使用DNA微阵列来识别在特定组织中表达的基因（由特定转录因子调节），通过特定细胞信号传导途径，通过程序性细胞死亡，通过在转基因动物中表达人类疾病基因的同源物或通过添加各种药物。微阵列数据将在我们的微阵列网站上展示和分析。我估计我们每年可以进行大约100个微阵列实验，与多达50个不同的实验室合作。我们的每个合作者都将通过确定两个突变菌株或生长条件之间的基因表达差异而受益，并可能设计后续实验来确定微阵列实验预测的靶基因表达模式的功能。斯坦福大学的微阵列中心将从每次合作中受益，因为它能够建立一个基因表达模式的全局矩阵，这样我们就可以分析基因表达的全局模式。未来两到三年是发展DNA微阵列技术的关键时期，秀丽隐杆线虫微阵列将在发展这项技术中发挥重要作用，因为这些微阵列将是唯一包含后生动物完整基因组的微阵列。

We are entering a new age in molecular genetics in which we can use sequence data from genome projects to dissect cell, developmental and disease pathways more completely and more sensitively than ever before. We need to develop new experimental approaches to analyze the vast amounts of data that are now available from genome projects. C. elegans is the only animal model system with a complete genome sequence, and thus will play a leading role in establishing approaches that make use of the full genome sequence. One key functional genomics approach is to use DNA microarrays to define changes in gene expression patterns during development and during the onset of disease. Our goal is to set up a center at Stanford for the worm academic community to perform DNA microarray experiments. To my knowledge, our lab is the only one that has C. elegans DNA microarrays, and so we are the only potential resource for DNA microarrays for the academic C. elegans community. We will plan DNA microarray experiments with our collaborators, and then perform DNA microarray experiments using RNA samples that they send to us. We are using DNA microarrays to identify genes that are expressed in specific tissues, regulated by specific transcription factors), by specific cell signaling pathways, by programmed cell death, by expression of homologs of human disease genes in transgenic animal or by addition of various pharmaceutical drugs. The microarray data will be presented and analyzed on our microarray website. I estimate that we can perform approximately 100 microarray experiments each year, collaborating with up to 50 different labs. Each of our collaborators will benefit by identifying gene expression differences between two mutant strains or growth conditions, and may design subsequent experiments to determine the function of expression pattern of target genes predicted by the microarray experiment. The microarray center at Stanford will benefit from each collaboration by being able to establish a global matrix of gene expression patters, so that we can analyze global patterns of gene expression. The next two to three years is a critical time to develop DNA microarray technology, and C. elegans microarrays can play an important part in developing this technology because these miroarrays will be the only one containing the complete genome from a metazoan.