high-content, image-based screening for drug targets in yeast含量高,基于图像的筛查药物靶点在酵母.pdfVIP

High-Content, Image-Based Screening for Drug Targets in Yeast Shinsuke Ohnuki, Satomi Oka, Satoru Nogami, Yoshikazu Ohya* Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan Abstract 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. Methodology: 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. Citation: Ohnuki S, Oka S, Nogami S, Ohya Y (2010) High-Content, Image-Based Screening for Drug Targets in Yeast. PLoS ONE 5(4): e10177. doi:10.1371/ journal.pone.0010177 Editor: Ben Lehner, Centre for Genomic Regulation, Spain Received February 3, 2010; Accepted March 25, 2010; Published April 14, 2010 Copyright: 2010 Ohnuki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite