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Optogenetic characterization methods overcome key challenges in synthetic and systems biology

Abstract

Systems biologists aim to understand how organism-level processes, such as differentiation and multicellular development, are encoded in DNA. Conversely, synthetic biologists aim to program systems-level biological processes, such as engineered tissue growth, by writing artificial DNA sequences. To achieve their goals, these groups have adapted a hierarchical electrical engineering framework that can be applied in the forward direction to design complex biological systems or in the reverse direction to analyze evolved networks. Despite much progress, this framework has been limited by an inability to directly and dynamically characterize biological components in the varied contexts of living cells. Recently, two optogenetic methods for programming custom gene expression and protein localization signals have been developed and used to reveal fundamentally new information about biological components that respond to those signals. This basic dynamic characterization approach will be a major enabling technology in synthetic and systems biology.

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Figure 1: Parallels between electrical and biological systems engineering.
Figure 2: Nonidealities in electronic components.
Figure 3: Challenges in characterizing biological components, circuits and systems.
Figure 4: Developing and using biological function generators to characterize biological components, circuits and systems.
Figure 5: Optogenetic reverse engineering of Ras-Erk signaling.
Figure 6: Forward engineering biological systems by optogenetic component characterization.

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Acknowledgements

We thank L.A. Hartsough for his comments on the manuscript. E.J.O. and J.J.T. are supported by the US National Science Foundation Biotechnology, Biochemical and Biomass Engineering (BBBE) program (EFRI–1137266) and the Office of Naval Research (ONR) Multidisciplinary University Research Initiative (MURI) program (N000141310074). J.J.T. is supported by the Defense Advanced Research Projects Agency Living Foundries Advanced Tools and Capabilities for Generalizable Platforms (ATCG) and ONR Young Investigator Programs.

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Olson, E., Tabor, J. Optogenetic characterization methods overcome key challenges in synthetic and systems biology. Nat Chem Biol 10, 502–511 (2014). https://doi.org/10.1038/nchembio.1559

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