This proposal to the National Center for Research Resources seeks funds to establish a state-of-the-art High Content Cell-based Screening System that would serve researchers in biomedical departments at the Emory University School of Medicine. As a group, the major and minor investigators supervise vigorous research programs, share complementary research interests, and are amply supported by NIH mechanisms. The requested instrument will bring together chemists and biomedical scientists in an environment that facilitates the discovery and study of novel small molecules that may ultimately lead to the development of novel therapeutic strategies. As the worldwide genome Initiatives near fruition, we recognize unique opportunities to significantly enhance and extend many of our current studies by incorporation of 96/384-well live-cell based assay strategies. A Molecular Devices Discovery-1 High Content Screening System and associated software and integrated fluidics form the core of this system, which will allow for rapid and systematic quantitative measurements of numerous cell biological events such as neurite outgrowth, cell viability, mitotic rate, mitochondrial dysfunction, receptor clustering, translocation of proteins between cellular compartments, angiogenesis, apoptosis, receptor internalization, exocytosis, cell motility, and others. The requested system will greatly facilitate studies supported by NIH. ? ?