Small-molecule screening and profiling by using automated microscopy.
Automated fluorescence microscopy provides a powerful tool for analyzing the physiological state of single cells with high throughput and high information content. Here I discuss two types of experiments in which this technology was used to discover and characterize bioactive small molecules. In phenotypic-screening experiments, the goal is to find "hits" with specific effects on cells by screening large libraries of small molecules. An example is screening for small molecules that perturb mitosis by novel mechanisms. In cytological-profiling experiments, the goal is to characterize the bioactivity of a limited number of small molecules in considerable depth, and thus understand their mechanism and toxicities at the cellular level. I discuss an example in which 100 small molecules with known bioactivity were profiled by using multiple fluorescent probes, and clustered into mechanistic classes by automated statistical analysis.
Mitchison
Timothy J
TJ
Dept. Systems Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA. timothy_mitchison@hms.harvard.edu
D000465:Algorithms; D001331:Automation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*