High-throughput screening of cellular features using high-resolution light-microscopy; Application for profiling drug effects on cell adhesion

Yael Paran, Micha Ilan, Yoel Kashman, Sofee Goldstein, Yuvalal Liron, Benjamin Geiger, Zvi Kam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

High-resolution light-microscopy and high-throughput screening are two essential methodologies for characterizing cellular phenotypes. Optimally combining these methodologies in cell-based screening to test detailed molecular and cellular responses to multiple perturbations constitutes a major challenge. Here we describe the development and application of a screening microscope platform that automatically acquires and interprets sub-micron resolution images at fast rates. The analysis pipeline is based on the quantification of multiple subcellular features and statistical comparisons of their distributions in treated vs. control cells. Using this platform, we screened 2200 natural extracts for their effects on the fine structure and organization of focal adhesions. This screen identified 15 effective extracts whose fractionation and characterization were further analyzed using the same microscope system. The significance of combining resolution, throughput and multi-parametric analyses for biomedical research and drug discovery is discussed.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalJournal of Structural Biology
Volume158
Issue number2
DOIs
StatePublished - May 2007

Funding

FundersFunder number
Clore Center for Biological Physics
Kahn Fund for Systems Biology
Yad Abraham Center for Cancer Diagnosis and Therapy
National Institutes of Health
National Institute of General Medical SciencesU54GM064346
Weizmann Institute of Science
Israel Science Foundation

    Keywords

    • Cell-based screening
    • Focal adhesion
    • High-resolution light-microscopy
    • Image analysis
    • Natural compounds

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