High-content, image-based screening for drug targets in yeast.
BACKGROUND
Drug discovery and development are predicated on elucidation of the potential mechanisms of action and cellular targets of candidate chemical compounds. Recent advances in high-content imaging techniques allow simultaneous analysis of a range of cellular events. In this study, we propose a novel strategy to identify drug targets by combining genetic screening and high-content imaging in yeast.


METHODS
In this approach, we infer the cellular functions affected by candidate drugs by comparing morphologic changes induced by the compounds with the phenotypes of yeast mutants.


CONCLUSIONS
Using this method and four well-characterized reagents, we successfully identified previously known target genes of the compounds as well as other genes involved with functionally related cellular pathways. This is the first demonstration of a genetic high-content assay that can be used to identify drug targets based on morphologic phenotypes of a reference mutant panel.
Ohnuki
Shinsuke
S
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
Oka
Satomi
S
Nogami
Satoru
S
Ohya
Yoshikazu
Y
D016503:Drug Delivery Systems; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019044:Image Cytometry / Q000379:methods*; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*