Understanding gene function and drug action

TOXI 145

Guri Giaever, guri.giaever@utoronto.ca, Department of Pharmaceutical Sciences, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Rm 1208, 160 College Street, Toronto, ON M5S3E1, Canada
The identification of drug targets and associated pathways is essential for gaining insight into the mechanism of drug action and for uncovering potential new pharmaceuticals. The budding yeast Saccharomyces cerevisiae has proven an effective model system for realizing these two aims. Because the yeast proteome shares ~50% homology to human compounds that are effective on yeast proteins they are often effective against their human counterparts. The number of genomic and proteomic tools for interrogating yeast is vast and growing. For example, complete libraries of gene knock-outs, over-expression strains, epitope and fluorescently labeled proteins are available. Such resources, combined with the extraordinary arsenal of genetic tools available provide a powerful foundation for a high throughput, genome-wide drug discovery effort. Here we summarize the successes of two methods, haploinsufficiency profiling (HIP) and homozygote profiling (HOP) aimed at drug target elucidation. Finally we provide a prospective for improving these assays and integrating them with other systems-levels approaches.