Mitchison Timothy J
Dept. Systems Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Chembiochem. 2005 Jan;6(1):33-9. doi: 10.1002/cbic.200400272.
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.
自动化荧光显微镜为高通量、高信息量地分析单细胞的生理状态提供了强大工具。在此，我将讨论两类实验，在这些实验中该技术被用于发现和表征生物活性小分子。在表型筛选实验中，目标是通过筛选小分子文库来找到对细胞有特定作用的“命中物”。一个例子是筛选通过新机制干扰有丝分裂的小分子。在细胞分析实验中，目标是深入表征有限数量小分子的生物活性，从而在细胞水平理解它们的作用机制和毒性。我将讨论一个例子，其中使用多种荧光探针分析了100种具有已知生物活性的小分子，并通过自动统计分析将它们聚类为不同的作用机制类别。
