The long-term aim of this research was to use functional and chemical genomic approaches to understand local and global relationships among genes, proteins and chemicals in the budding yeast Saccharomyces cerevisiae.

The project team used cutting-edge functional genomics to define gene function and to probe the mechanistic basis for drug action and the characterization of novel, unknown, and microbial proteins. The project used a multidisciplinary approach to characterize the relationships among genes, proteins and chemicals. To examine how an essential gene affects global gene expression, the investigators replaced the promoter in 773 essential genes with a new promoter that could be experimentally regulated. To expand the genetic-interaction network, the investigators employed the synthetic genetic array (SGA) system, which automates yeast genetic analysis.

The essential gene project produced 773 regulatable yeast strains for 773 essential genes – a resource that allowed investigators to generate profiles describing the chemical sensitivity, morphology and gene expression of yeast, providing insight into protein and cell function. The SGA project lead to the expansion of a genetic-interaction network to include approximately 4000 digenic interactions involving approximately 1000 genes, as well as a second network of 567 interactions involving essential genes. The group was also able to generate 206 protein structures for unknown proteins. This basic research provided an approach for understanding more complex systems, which may be applied to understanding and treating human disease.

The investigators also generated one of the most cited papers in the field of molecular biology/genetics during the course of the project (Science, 2004) and established more than 85 collaborations. The information ascertained from this project has greatly extended fundamental knowledge about microbial biology and created an experimental basis for the Canadian biotech industry to develop anti-microbial drugs and biotechnological processes.