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Programmable cells: interfacing natural and engineered gene networks.

Hideki Kobayashi1, Mads Kaern, Michihiro Araki

  • 1Department of Biomedical Engineering, Center for BioDynamics, and Center for Advanced Biotechnology, Boston University, 44 Cummington Street, Boston, MA 02215, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 26, 2004
PubMed
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Engineered gene circuits enable programmable cellular behaviors. Researchers created Escherichia coli with genetic toggle switches that respond to DNA damage or cell density, demonstrating a step toward plug-and-play genetic circuitry.

Area of Science:

  • Synthetic biology
  • Genetic engineering
  • Microbiology

Background:

  • Cells possess natural regulatory circuits that control their behavior.
  • Engineered gene networks can be coupled to these natural circuits to create novel cellular functions.
  • Programmable cellular responses are crucial for various biotechnological applications.

Purpose of the Study:

  • To demonstrate the use of an engineered genetic circuit for creating cells with predetermined and programmable responses to biological signals.
  • To engineer Escherichia coli strains with specific responses to DNA damage and cell population density.

Main Methods:

  • A modular design strategy was employed to create Escherichia coli strains.
  • A genetic toggle switch was interfaced with the SOS signaling pathway (DNA damage response) and a quorum sensing signaling pathway from Vibrio fischeri.

Related Experiment Videos

  • The engineered strains were analyzed for their response dynamics and phenotypic alterations.
  • Main Results:

    • The engineered genetic toggle switch provided binary response dynamics and epigenetic inheritance.
    • Escherichia coli strains were successfully engineered to form biofilms in response to DNA-damaging agents.
    • Cells were programmed to activate protein synthesis upon reaching a critical population density.

    Conclusions:

    • Engineered genetic circuitry can confer programmable behaviors onto cells.
    • The developed "plug-and-play" genetic circuit approach facilitates the creation of cells with tailored functionalities.
    • This work advances the development of synthetic biological systems for precise cellular control.