Charlie Boone
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Professor |
Charlie Boone |
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Abstract: My lab develops yeast functional genomics approaches for global interrogation of the roles of genes and pathways. In particular, we are attempting to generate a large-scale genetic interaction map for yeast cells, in which we create all possible double mutants and score them for a synthetic lethal phenotype [Tong et al., Science 295:321-324 (2002)]. Genes with similar genetic interaction profiles often occur in the same pathway or complex and thus clustering of large-scale genetic interaction data identifies complexes and pathways [Tong et al., Science 303:808-813 (2004)]. Moreover, because genetic interactions are largely orthogonal to protein-protein interactions the genetic network complements protein-protein interaction maps, adding functional information to the physical network. Because a gene deletion mutant is a good model for the activity of an inhibitory compound, the synthetic lethal network is a key for interpreting chemical-genetic profiles in which the set of ~5000 viable yeast deletion mutants are tested for hypersensitivity to a specific compound, providing a new way of linking bioactive compounds to their intracellular targets [Parsons et al., Nat. Biotech 22: 62-69 (2004)]. In a large-scale analysis of chemical-genetic profiles, we also showed that clustering of these profiles links compounds of similar function, just as we observed for genetic interaction networks [Parsons et al., Cell 126: 611-625 (2006)].
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