Comprehensive discovery of genetic mechanisms of drug resistance and identification of in vivo drug targets represent significant challenges. Here we present a functional variomics technology in the model organism Saccharomyces cerevisiae. This tool analyzes numerous genetic variants and effectively tackles both problems simultaneously. Using this tool, we discovered almost all genes that, due to mutations or modest overexpression, confer resistance to rapamycin, cycloheximide, and amphotericin B. Most significant among the resistance genes were drug targets, including multiple targets of a given drug. With amphotericin B, we discovered the highly conserved membrane protein Pmp3 as a potent resistance factor and a possible target. Widespread application of this tool should allow rapid identification of conserved resistance mechanisms and targets of many more compounds. New genes and alleles that confer resistance to other stresses can also be discovered. Similar tools in other systems, such as human cell lines, will also be useful.
Pubmed ID: 23416056 RIS Download
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A curated database that provides comprehensive integrated biological information for Saccharomyces cerevisiae along with search and analysis tools to explore these data. SGD allows researchers to discover functional relationships between sequence and gene products in fungi and higher organisms. The SGD also maintains the S. cerevisiae Gene Name Registry, a complete list of all gene names used in S. cerevisiae which includes a set of general guidelines to gene naming. Protein Page provides basic protein information calculated from the predicted sequence and contains links to a variety of secondary structure and tertiary structure resources. Yeast Biochemical Pathways allows users to view and search for biochemical reactions and pathways that occur in S. cerevisiae as well as map expression data onto the biochemical pathways. Literature citations are provided where available.
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