Rational design of memory in eukaryotic cells

  1. Caroline M. Ajo-Franklin1,3,4,
  2. David A. Drubin1,3,
  3. Julian A. Eskin1,
  4. Elaine P.S. Gee2,
  5. Dirk Landgraf1,
  6. Ira Phillips1,5, and
  7. Pamela A. Silver1,6
  1. 1 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
  2. 2 Harvard University Program in Biophysics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  1. 3 These authors contributed equally to this work.

Abstract

The ability to logically engineer novel cellular functions promises a deeper understanding of biological systems. Here we demonstrate the rational design of cellular memory in yeast that employs autoregulatory transcriptional positive feedback. We built a set of transcriptional activators and quantitatively characterized their effects on gene expression in living cells. Modeling in conjunction with the quantitative characterization of the activator-promoter pairs accurately predicts the behavior of the memory network. This study demonstrates the power of taking advantage of components with measured quantitative parameters to specify eukaryotic regulatory networks with desired properties.

Keywords

Footnotes

  • 4 Present addresses: Lawrence Berkeley National Laboratories, 1 Cyclotron Rd., MS 67R5110, Berkeley, CA 94720, USA;

  • 5 Vanderbilt Medical School, 201 Light Hall, Nashville, TN 37232, USA.

  • 6 Corresponding author.

    6 E-MAIL pamela_silver{at}hms.harvard.edu; FAX (617) 432-5201.

  • Supplemental material is available at http://www.genesdev.org.

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1586107

    • Received June 22, 2007.
    • Accepted July 27, 2007.
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