The Automated Cell: Compound and Environment Screening System (ACCESS) for Chemogenomic Screening
The automated cell, compound and environment screening system (ACCESS) was developed as an automated platform for chemogenomic research. In the yeast Saccharomyces cerevisiae, a number of genomic screens rely on the modulation of gene dose to determine the mode of action of bioactive compounds or the effects of environmental/compound perturbations. These and other phenotypic experiments have been shown to benefit from high-resolution growth curves and a highly automated controlled environment system that enables a wide range of multi-well assays that can be run over many days without any manual intervention. Furthermore, precise control of drug dosing, timing of drug exposure, and precise timing of cell harvesting at specific generation times are important for optimal results. Some of these benefits include the ability to derive fine distinctions between growth rates of mutant strains (1) and the discovery of novel compounds and drug targets (2). The automation has also enabled large-scale screening projects with over 100,000 unique compounds screened to date including a thousand genome-wide screens (3). The ACCESS system also has a diverse set of software tools to enable users to set up, run, annotate, and evaluate complex screens with minimal training.
Key wordsRobotics phenotypic screening genome-wide screening yeast bacteria drug discovery
The authors would like to thank Bob St. Onge (Stanford HIPHOP lab) for suggestions for the continued development of the ACCESS robots; Larry Heisler (Toronto HIPHOP lab) for development of the Infinite conversion scripts and web site tools; Pinay Kainth from the University of Toronto for the generous gift of the HT1A-GFP strains; Mark Torresan (Tecan USA) for many years of helpful advice and support; and Susan Dutcher (Washington University School of Medicine) for C. reinhardtii strains and advice. Finally, we would like to thank all past and present members of the Stanford and Toronto HIPHOP laboratories for their feedback, support, and innovative use of the ACCESS robots. This work was supported by grants from NIH (NCI, NBIB, and NHGRI) and CIHR to R.W.D., C.N., and G.G, and from the Canadian Cancer Society (020380) to G.G.