Programming Escherichia coli to function as a digital display

Synthetic genetic circuits offer the potential to wield computational control over biology, but their complexity is limited by the accuracy of mathematical models. Here, we present advances that enable the complete encoding of an electronic chip in the DNA carried by Escherichia coli (E. coli). The...

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Main Authors: Shin, Jonghyeon, Zhang, Shuyi, Der, Bryan S., Nielsen, Alec, Voigt, Christopher A.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: EMBO 2020
Online Access:https://hdl.handle.net/1721.1/125334
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author Shin, Jonghyeon
Zhang, Shuyi
Der, Bryan S.
Nielsen, Alec
Voigt, Christopher A.
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Shin, Jonghyeon
Zhang, Shuyi
Der, Bryan S.
Nielsen, Alec
Voigt, Christopher A.
author_sort Shin, Jonghyeon
collection MIT
description Synthetic genetic circuits offer the potential to wield computational control over biology, but their complexity is limited by the accuracy of mathematical models. Here, we present advances that enable the complete encoding of an electronic chip in the DNA carried by Escherichia coli (E. coli). The chip is a binary-coded digit (BCD) to 7-segment decoder, associated with clocks and calculators, to turn on segments to visualize 0-9. Design automation is used to build seven strains, each of which contains a circuit with up to 12 repressors and two activators (totaling 63 regulators and 76,000 bp DNA). The inputs to each circuit represent the digit to be displayed (encoded in binary by four molecules), and output is the segment state, reported as fluorescence. Implementation requires an advanced gate model that captures dynamics, promoter interference, and a measure of total power usage (RNAP flux). This project is an exemplar of design automation pushing engineering beyond that achievable "by hand", essential for realizing the potential of biology.
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spelling mit-1721.1/1253342022-10-01T04:40:21Z Programming Escherichia coli to function as a digital display Shin, Jonghyeon Zhang, Shuyi Der, Bryan S. Nielsen, Alec Voigt, Christopher A. Massachusetts Institute of Technology. Department of Biological Engineering Synthetic genetic circuits offer the potential to wield computational control over biology, but their complexity is limited by the accuracy of mathematical models. Here, we present advances that enable the complete encoding of an electronic chip in the DNA carried by Escherichia coli (E. coli). The chip is a binary-coded digit (BCD) to 7-segment decoder, associated with clocks and calculators, to turn on segments to visualize 0-9. Design automation is used to build seven strains, each of which contains a circuit with up to 12 repressors and two activators (totaling 63 regulators and 76,000 bp DNA). The inputs to each circuit represent the digit to be displayed (encoded in binary by four molecules), and output is the segment state, reported as fluorescence. Implementation requires an advanced gate model that captures dynamics, promoter interference, and a measure of total power usage (RNAP flux). This project is an exemplar of design automation pushing engineering beyond that achievable "by hand", essential for realizing the potential of biology. Office of Naval Research (Grant N00014-16-1-2388) US National Institute of General Medical Sciences (NIGMS) (Grant P50-GM098792) National Science Foundation (NSF) (Grant CCF-1807575) DARPA (Grant SD2-FA8750-17-C-0229) 2020-05-19T21:25:01Z 2020-05-19T21:25:01Z 2020-03 2020-02 2020-03-18T15:15:29Z Article http://purl.org/eprint/type/JournalArticle 1744-4292 1744-4292 https://hdl.handle.net/1721.1/125334 Shin, Jonghyeon et al. "Programming Escherichia coli to function as a digital display." Molecular Systems Biology 16, 3 (March 2020): e9401 en http://dx.doi.org/10.15252/msb.20199401 Molecular Systems Biology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf EMBO Molecular Systems Biology
spellingShingle Shin, Jonghyeon
Zhang, Shuyi
Der, Bryan S.
Nielsen, Alec
Voigt, Christopher A.
Programming Escherichia coli to function as a digital display
title Programming Escherichia coli to function as a digital display
title_full Programming Escherichia coli to function as a digital display
title_fullStr Programming Escherichia coli to function as a digital display
title_full_unstemmed Programming Escherichia coli to function as a digital display
title_short Programming Escherichia coli to function as a digital display
title_sort programming escherichia coli to function as a digital display
url https://hdl.handle.net/1721.1/125334
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