The completion of the yeast genome sequence in April 1996 inaugurated the era of genome-wide exploration of gene function. The goal of this project is to produce a detailed """"""""functional map"""""""" of the yeast genome. A great many functional attributes can naturally be mapped onto the framework that the genome sequence provides. The overarching goal is to map onto this framework any kind of information that might be useful in understanding the genome, and understanding how the static information in the genome sequence comes to life in the living organism. Most of the proposed work relies on the DNA microarray technology that was developed in this laboratory a few years ago, which provides a convenient, versatile and economical tool for investigating diverse properties of genes and DNA sequences on a genome-wide basis. Three principal projects are envisioned: 1. A comprehensive survey of global gene expression programs. The effects on expression of every yeast gene of thousands of conditions, including diverse environmental and genetic perturbations as well as endogenous genetic programs, will be determined. A systematic survey will be conducted, aimed at identifying the target genes regulated by each putative regulatory gene in the yeast genome. Computational tools, already under development, will be used to draw inferences of function from the patterns of expression of each gene, and to identify candidate cis-regulatory elements that account for the observed expression patterns. 2. A detailed map of the in vivo pattern of protein binding to the yeast genome will be developed. 3. A new microarray-based method for analyzing the consequences of dominant mutations on a genomic scale will be developed. This procedure will be applied initially to define the consequences of overexpression of each yeast gene on fitness under a diverse set of selective conditions. Throughout the course of this work, we will continue our ongoing efforts to invent and discover new ways to use DNA microarray technology and other experimental approaches to explore the genome.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000983-06
Application #
6388306
Study Section
Genome Study Section (GNM)
Program Officer
Feingold, Elise A
Project Start
1996-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2003-04-30
Support Year
6
Fiscal Year
2001
Total Cost
$531,703
Indirect Cost
Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Dunham, Maitreya J; Badrane, Hassan; Ferea, Tracy et al. (2002) Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 99:16144-9
Trotter, Eleanor W; Kao, Camilla M-F; Berenfeld, Ludmilla et al. (2002) Misfolded proteins are competent to mediate a subset of the responses to heat shock in Saccharomyces cerevisiae. J Biol Chem 277:44817-25
Wang, Yulei; Liu, Chih Long; Storey, John D et al. (2002) Precision and functional specificity in mRNA decay. Proc Natl Acad Sci U S A 99:5860-5
Yoshimoto, Hiroyuki; Saltsman, Kirstie; Gasch, Audrey P et al. (2002) Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. J Biol Chem 277:31079-88
Rutherford, J C; Jaron, S; Ray, E et al. (2001) A second iron-regulatory system in yeast independent of Aft1p. Proc Natl Acad Sci U S A 98:14322-7
Courcelle, J; Khodursky, A; Peter, B et al. (2001) Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 158:41-64
Rothenberg, S M; Olsen, M N; Laurent, L C et al. (2001) Comprehensive mutational analysis of the Moloney murine leukemia virus envelope protein. J Virol 75:11851-62
Gasch, A P; Huang, M; Metzner, S et al. (2001) Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell 12:2987-3003
Wendisch, V F; Zimmer, D P; Khodursky, A et al. (2001) Isolation of Escherichia coli mRNA and comparison of expression using mRNA and total RNA on DNA microarrays. Anal Biochem 290:205-13
Ogawa, N; DeRisi, J; Brown, P O (2000) New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Mol Biol Cell 11:4309-21

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