Cell Arrays for Measuring Gene Function on a Genomic Scale

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Cell Arrays for Measuring Gene Function on a
Genomic Scale

• Edward Marcotte, Ph.D.
• Department of Chemistry and Biochemistry

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Cell-based assays

• Replacing traditional enzyme or antibody-based
  assays
• The cell is the minimum physiological unit in the
  body.
• Greater accuracy is obtained when measuring drug
  action.
• Activity is monitored in the context of a living,
  dynamic environment.

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Opportunities and challenges

• Cell-based assays are central to
• Drug discovery programs
• Toxicology and initial ADME studies
• Drug re-work efforts
• Cell-based assays have inherent limitations.
• Capacity of samples
• Adaptability to new assays
• Need to meet expanding market
• Cell-based assay market is gt1 billion/year.

Genetic Engineering News
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A new approach to cell-based assays
OR
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Our solution

• A cell-based chip
• Array up to 10,000 different cell variants on a
  microslide
• Map coordinates of cell spots
• Perform desired assay
• Applications
• Analyze multiple drugs on single cell type
• Analyze single drug on thousands of cell types
• Living or fixed cells
• Simultaneous analysis of
• Entire bacteria or yeast knockout libraries
• Human RNAi knock-down libraries
• Human/yeast GFP-tagged protein libraries

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Cell chip fabrication
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Example Protein subcellular localization
GFP-taggedcell library
gt500,000 assays performed to date
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Benefits

• Applicable with bacterial, yeast, and mammalian
  cells
• Small amounts of reagents expended
• Enabling rare cell and limited compound analysis
• Amenable to many assays
• Protein localization and dynamic transport
• High-content, fluorescence assays
• Drug effect assays, cyto-toxicity
• Apoptosis
• Cell proliferation
• Flexible format, easy storage
• Applications in drug discovery and genetic
  network research
• U.S. and PCT patents filed covering technology