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Engineered gene circuits

Abstract

A central focus of postgenomic research will be to understand how cellular phenomena arise from the connectivity of genes and proteins. This connectivity generates molecular network diagrams that resemble complex electrical circuits, and a systematic understanding will require the development of a mathematical framework for describing the circuitry. From an engineering perspective, the natural path towards such a framework is the construction and analysis of the underlying submodules that constitute the network. Recent experimental advances in both sequencing and genetic engineering have made this approach feasible through the design and implementation of synthetic gene networks amenable to mathematical modelling and quantitative analysis. These developments have signalled the emergence of a gene circuit discipline, which provides a framework for predicting and evaluating the dynamics of cellular processes. Synthetic gene networks will also lead to new logical forms of cellular control, which could have important applications in functional genomics, nanotechnology, and gene and cell therapy.

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Figure 1: Autoregulatory systems.
Figure 2: Natural and synthetic co-repressive switches.
Figure 3: Logic gates.
Figure 4: Synthetic transcriptional oscillator (the repressilator14).
Figure 5: Synthetic oscillator design and synchronization properties.

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Acknowledgements

This work was supported by the Defense Advanced Research Projects Agency (DARPA), Office of Naval Research (ONR), National Science Foundation (NSF) BioQuBIC, the Fetzer Institute, and Natural Sciences and Engineering Research Council of Canada (NSERC).

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Correspondence to Jeff Hasty.

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Hasty, J., McMillen, D. & Collins, J. Engineered gene circuits. Nature 420, 224–230 (2002). https://doi.org/10.1038/nature01257

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