Since they are hardy and flourish even outside the body, the Harvard team used human cancer cells. They placed the cells in 384 minuscule wells in a plastic dish, injected each well with one of 100 drugs -- both medicines and toxins -- at different concentrations, and finished off the plates with11 chemical probes for different proteins and DNA.
After 20 hours of cell growth, the researchers used automated microscopy to collect some half a million images of the treated cells, followed by approximately 5 billion individual measurements of the size, shape, and quantity of different proteins, DNA, and organelles in each. Software developed by Altschuler, Wu, and colleagues allowed them to convert this copious data into profiles of the effects of each drug, yielding distinctive red-and-green "fingerprints" for each, not unlike the color-coded data from a DNA chip.
However, unlike DNA chips that meld bountiful data into an "average" denoted by dots of color on a grid, cytological profiling preserves individual data points -- so researchers can go back and analyze fine-grain information.
"By allowing quantitative measurement of many proteins and structures in cells over many samples, and systematic comparison between samples, our method brings microscopy into the '-omics' era, like genomics and proteomics," says Mitchison, of Harvard Medical School's Institute of Chemistry and Cell Biology and Department of Systems Biology. "This really allows us a much broader view of how cells are affected by a wide range of perturbations."
Cytological profiling may be especially useful, Mitchison says, for evaluating dru
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Contact: Steve Bradt
steve_bradt@harvard.edu
617-496-8070
Harvard University
11-Nov-2004