| STUDY |
environmental stressors are far more complex than previously thought. Leona Samson, professor of biological engineering and toxicology at Massachusetts Institute of Technology, employs an approach known as genomic phenotyping to study how toxic exposures affect the yeast Saccharomyces cerevisiae. Saccharomyces was the first organism to have all its genes--some 6,000--sequenced. Researchers have now assembled a library of knockout mutant yeasts, in which each strain has one gene deleted. Researchers can use the mutants to help deduce the importance of certain genes in surviving environmental stress. Samson's lab used a semirobotic system in which they placed about 1,650 knockout strains, along with a wild-type strain, onto plates with arrays of agar dots. They exposed each strain to several different doses each of methyl methanesulfonate, tert-butyl hydroperoxide, 4-nitroquinoline-N-oxide, and ultraviolet light, all of them DNA-damaging agents. They then watched to see how the strains, with their different missing genes, fared. Surprisingly, a great number of strains were sensitive to the compounds. When they first started the experiment, Samson said, they knew of but a few dozen genes that were important in helping an organism to recover from exposure to a DNA-damaging agent. But as they soon discovered, those genes are only part of the story. Oddly, they found little correlation between whether a gene altered its expression in response to a compound and whether a strain missing that gene was sensitive or resistant to the lethal effects of the DNA-damaging compounds. "We were very surprised," Samson said. They began examining protein-protein interaction databases and developed programs to merge the interaction data with their genomics database. The combination uncovered whole networks of proteins involved in helping the cells recover. DNA-damage-repair proteins are present in the networks, but not as many as expected, Samson said. Other proteins, such as the product of RNA-processing genes, are also very important in the DNA-damage-repair process. Samson's group has now tested 4,800 of the yeast strains and has created an "interactome" database, involving 5,000 proteins and 20,000 interactions. "Pathways you've been concentrating on for the past two or three decades turn out to be only one or two among many, many important pathways," Samson said. |
| UPDATE | 03.03 |
| AUTHOR | MIT s Samson Leona |
| LITERATURE REF. | This data is not available for free |
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