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Programmable full-adder computations in communicating three-dimensional cell cultures

Nature Methods volume 15, pages 5760 (2018) | Download Citation

Abstract

Synthetic biologists have advanced the design of trigger-inducible gene switches and their assembly into input-programmable circuits that enable engineered human cells to perform arithmetic calculations reminiscent of electronic circuits. By designing a versatile plug-and-play molecular-computation platform, we have engineered nine different cell populations with genetic programs, each of which encodes a defined computational instruction. When assembled into 3D cultures, these engineered cell consortia execute programmable multicellular full-adder logics in response to three trigger compounds.

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Acknowledgements

We thank T. Horn, E. Montani and A. Ponti for assistance with microscopy and fluorescence analysis. We are grateful to M. Müller, F. Sedlmayer, D. Fuchs, T. Strittmatter and H. Kim for generous advice; C. Kemmer (Bioversys AG, Basel, Switzerland) for providing plasmids before publication; and D. Fluri (Insphero AG, Zurich, Switzerland) for support with GravityTRAP plates. This work was financially supported in part through a European Research Council (ERC) advanced grant (ProNet, no. 321381) and in part by the National Centre of Competence in Research (NCCR) for Molecular Systems Engineering.

Author information

Affiliations

  1. Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.

    • David Ausländer
    • , Simon Ausländer
    • , Xavier Pierrat
    • , Leon Hellmann
    • , Leila Rachid
    •  & Martin Fussenegger
  2. Faculty of Science, University of Basel, Basel, Switzerland.

    • Martin Fussenegger

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Contributions

D.A. and S.A. designed the project. D.A., S.A. and M.F. analyzed the results and wrote the manuscript. D.A., S.A., X.P., L.H. and L.R. performed the experimental work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Martin Fussenegger.

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DOI

https://doi.org/10.1038/nmeth.4505