GLOBAL PHENOTYPE ANALYSIS SYSTEM FOR GENOMIC RESEARCH

截至1997年9月，12种微生物的全基因组序列已 代表细胞生命的所有三个领域。的 对应于ORF的基因的注释很大程度上依赖于序列 来自最好研究的微生物（例如E. coli，B.枯草芽孢杆菌（S. 酿酒酵母）或从克隆到E.杆菌 然而，即使进行了大量的推断， 而“归属功能”的范围仅为44%至69%。最 当前迫切需要开发高效、经济、 用于确定基因功能的可靠技术（功能性 基因组学）。迄今为止发展起来的技术强调分子生物学 方法。本项目的目标是开发一个 细胞方法来解决这个问题，包括一个仪器使用 廉价的一次性测试板，这将允许生物学家 直接并同时测定细胞系中 表型。在第一阶段，我们将重点开发用于 E.杆菌在第二阶段，我们将扩大工作范围，并包括同等的努力 在S.啤酒。这些原核和真核微生物将 作为其它类型细胞的基因组模型 细胞 拟定商业应用： 基因组分析是非常重要的，并收到了相当大的一部分 政府和大学科研预算的合理性 NIH和DOE资助的实验室，以及基因组学公司、生物技术 公司和制药公司。因此，我们期望 测试系统的重要市场 这个提议。

As of September, 1997 the complete genome sequences of 12 microbes had been obtained representing all three domains of cellular life. The annotation of genes corresponding to ORFs relies heavily on sequence data from the best studied microbes (e.g. E. coli, B. subtilis, and S. cerevisiae) or from heterologous sequences that are cloned into E. coli. Yet even with a great deal of extrapolation, the percentage of genes with an "ascribed function" ranges from only 44% to 69%. The most pressing current need is to develop efficient, cost-effective, and reliable technologies for determining the function of genes (functional genomics). Technologies developed thus far have emphasized molecular approaches. The goal of this project is to develop a complementary cellular approach to this problem consisting of an instrument using inexpensive disposable testing panels that will allow biologists to assay cell lines directly and simultaneously for thousands of phenotypes. In Phase I we will focus on developing testing panels for E. coli. In Phase II we will expand the work and include an equal effort on S. cerevisiae. These procaryotic and eucaryotic microorganisms will serve as genomic models for other types of cells including mammalian cells. PROPOSED COMMERCIAL APPLICATION: Genomic analysis is very important and receiving a substantial portion of the research budget in government and university research laboratories funded by NIH and DOE, and in genomics companies, biotech companies, and pharmaceutical companies. We therefore anticipate a significant market for the testing system that would be developed under this proposal.