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A synthetic genetic circuit whose signal-response curve is temperature-tunable from band-detection to sigmoidal behaviour

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Abstract

Programming new cellular functions by using synthetic gene circuits is a key goal in synthetic biology, and an important element of this process is the ability to couple to the information processing systems of the host cell using synthetic systems with various signal-response characteristics. Here, we present a synthetic gene system in Escherichia coli whose signal-response curve may be tuned from band detection (strongest response within a band of input concentrations) to a switch-like sigmoidal response, simply by altering the temperature. This change from a band-detection response to a sigmoidal response has not previously been implemented. The system allows investigation of a range of signal-response behaviours with minimal effort: a single system, once inserted into the cells, provides a range of response curves without any genetic alterations or replacement with other systems. By altering its output, the system may couple to other synthetic or natural genetic circuits, and thus serve as a useful modular component. A mathematical model has also been developed which captures the essential qualitative behaviours of the circuit.

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Abbreviations

EGFP:

Enhanced green fluorescent protein

PCR:

Polymerase chain reaction

IPTG:

Isopropyl β-d-1-thiogalactopyranoside

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Acknowledgements

This work was funded by the Natural Sciences and Engineering Research Council (NSERC, Discovery grant) of Canada, the Canada Foundation for Innovation (CFI, New Opportunities and Infrastructure Operating Fund grants), the Ontario Photonics Consortium (OPC), the Canadian Institutes for Health Research (CIHR, Tools, Techniques, and Devices grant), and the Ontario Research Fund (ORF).

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  1. Department of Chemical and Physical Sciences, Institute for Optical Sciences, University of Toronto Mississauga, 3359 Mississauga Rd. N, Mississauga, ON, L5L 1C6, Canada

    Sangram Bagh & David R. McMillen

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  1. Sangram Bagh
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  2. David R. McMillen
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Correspondence to David R. McMillen.

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Bagh, S., McMillen, D.R. A synthetic genetic circuit whose signal-response curve is temperature-tunable from band-detection to sigmoidal behaviour. Nat Comput 9, 991–1006 (2010). https://doi.org/10.1007/s11047-009-9167-3

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