Global Mapping of Genetic and Chemical-Genetic Networks in Yeast

Abstract

※ 5:15-6:00 PM coffee and informal discussion （Conference room at 2nd FL, GRC） Synthetic Genetic Array (SGA) analysis automates yeast genetics, enabling a number of different large-scale/systematic studies. In one of our major projects, we are attempting to generate the complete synthetic genetic interaction map for yeast cells in which all possible double mutants are constructed and tested for unexpected fitness defects. This map can be used to define complexes and pathways in the cell, but perhaps more importantly, it adds functional information to the protein-protein interaction map, identifying complexes and pathways that work together and buffer one another. Because a gene deletion mutation provides a model for the effect a target-specific inhibitor, the genetic network provides a key for interpreting chemical-genetic interaction profiles, which derived from testing the set of ~5000 viable yeast deletion mutants for hypersensitivity to a bioactive compound. To expand our genetic and chemical-genetic approaches in yeast, we are constructing a library of all yeast genes in a barcoded vector system, enabling highly parallel approaches for dosage suppression, dosage lethality, cloning by complementation and numerous other assays.