Yeast as a model eukaryote in toxinology: a functional genomics approach to studying the molecular basis of action of pharmacologically active molecules

Abstract

Yeast Saccharomyces cerevisiae has proven to be a relevant and convenient model organism for the study of diverse biological phenomena, due to its straightforward genetics, cost-effectiveness and rapid growth, combined with the typical characteristics of a eukaryotic cell. More than 40% of yeast proteins share at least part of their primary amino acid sequence with the corresponding human protein, making yeast a valuable model in biomedical research. In the last decade, high-throughput and genome-wide experimental approaches developed in yeast have paved the way to functional genomics that aims at a global understanding of the relationship between genotype and phenotype. In this review we first present the yeast strain and plasmid collections for genome-wide experimental approaches to study complex interactions between genes, proteins and endo- or exogenous small molecules. We describe methods for protein-protein, protein-DNA, genetic and chemo-genetic interactions, as well as localization studies, focussing on their application in research on small pharmacologically active molecules. Next we review the use of yeast as a model organism in neurobiology, emphasizing work done towards elucidating the pathogenesis of neurodegenerative diseases and the mechanism of action of neurotoxic phospholipases A(2).