An active intracellular device to prevent lethal disease outcomes in virus-infected bacterial cells

Authors

  • Sangram Bagh,

    1. Department of Chemical and Physical Sciences and Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd, Mississauga, Ontario, Canada L5L 1C6; telephone: (905) 828-5353; fax: (905) 828-5425
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  • Mahuya Mandal,

    1. Department of Chemical and Physical Sciences and Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd, Mississauga, Ontario, Canada L5L 1C6; telephone: (905) 828-5353; fax: (905) 828-5425
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  • Jordan Ang,

    1. Department of Chemical and Physical Sciences and Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd, Mississauga, Ontario, Canada L5L 1C6; telephone: (905) 828-5353; fax: (905) 828-5425
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  • David R. McMillen

    Corresponding author
    1. Department of Chemical and Physical Sciences and Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd, Mississauga, Ontario, Canada L5L 1C6; telephone: (905) 828-5353; fax: (905) 828-5425
    • Department of Chemical and Physical Sciences and Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd, Mississauga, Ontario, Canada L5L 1C6; telephone: (905) 828-5353; fax: (905) 828-5425.
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Abstract

Synthetic biology includes an effort to logically control cellular behavior. One long-term goal is to implement medical interventions inside living cells, creating intracellular “disease fighters”; one may imagine a system that detects viral infection and responds to halt the spread of the virus. Here, we explore a system designed to display some of the qualitative features that such disease prevention systems should have, while not claiming that the system itself has any medical application. An intracellular disease prevention mechanism should: lie dormant in the absence of the disease state; detect the onset of a lethal disease pathway; respond to halt or mitigate the disease's effects; and be subject to external deactivation when required. We have created a device that displays these properties, in the highly simplified case of a bacterial viral disease. Our system detects the onset of the lytic phase of bacteriophage lambda in Escherichia coli, responds by preventing this lethal pathway from being followed, and is deactivated by a temperature shift. We have formulated a mathematical model of the engineered system, using parameters obtained from the literature and by local experimental measurement, and shown that the model captures the essential experimental behavior of the system in most parameter regimes. Biotechnol. Bioeng. 2011; 108:645–654. © 2010 Wiley Periodicals, Inc.

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