Programming Escherichia coli to function as a digital display.

Molecular Systems Biology
Jonghyeon ShinChristopher A Voigt

Abstract

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.

References

Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·U DeuschleH Bujard
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A SellittiD A Steege
Nov 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yohei YokobayashiFrances H Arnold
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nicolas E BuchlerTerence Hwa
Sep 13, 2003·The EMBO Journal·Vitaly EpshteinEvgeny Nudler
Aug 3, 2004·Biotechnology and Bioengineering·Beat P KramerMartin Fussenegger
Jan 27, 2005·Journal of Molecular Biology·Kim SneppenJ Barry Egan
May 23, 2007·Nature Biotechnology·Keller RinaudoYaakov Benenson
Aug 19, 2007·Molecular Systems Biology·J Christopher AndersonAdam P Arkin
Nov 16, 2007·Molecular Systems Biology·Robert Sidney CoxMichael B Elowitz
Feb 16, 2008·Molecular Systems Biology·Domitilla Del VecchioEduardo D Sontag
Jul 10, 2008·Nature Biotechnology·Barry CantonDrew Endy
Mar 21, 2009·Journal of Biological Engineering·Jason R KellyDrew Endy
Aug 8, 2009·Physical Review Letters·Vincent DahirelJean-Marc Victor
Oct 6, 2009·Nature Chemical Biology·Cheemeng TanLingchong You
Apr 17, 2010·Nature Reviews. Genetics·Ahmad S Khalil, James J Collins
Nov 3, 2010·Journal of Biological Engineering·Sean C SleightHerbert M Sauro
Jun 13, 2012·Nature Reviews. Genetics·Yaakov Benenson
Oct 9, 2012·Nature·Tae Seok MoonChristopher A Voigt
Mar 30, 2013·Science·Jerome BonnetDrew Endy
May 10, 2013·ACS Synthetic Biology·Shridhar JayanthiDomitilla Del Vecchio
Dec 10, 2013·Nature Chemical Biology·Brynne C StantonChristopher A Voigt
Feb 6, 2014·Current Opinion in Biotechnology·Stefan Klumpp, Terence Hwa
May 2, 2014·Nature Methods·Jennifer A N Brophy, Christopher A Voigt
May 6, 2014·Current Opinion in Biotechnology·Oliver Purcell, Timothy K Lu
Jun 14, 2014·Science·Jeffrey W Roberts
Nov 25, 2014·Cell·Alexander A GreenPeng Yin
Nov 25, 2014·Nature Biotechnology·Deepak MishraRon Weiss
Nov 26, 2014·Molecular Systems Biology·Alec A K Nielsen, Christopher A Voigt
Jun 23, 2015·ACS Synthetic Biology·Benjamin R JackJeffrey E Barrick
Nov 10, 2015·ACS Synthetic Biology·Jesús Fernández-RodríguezChristopher A Voigt
Jan 16, 2016·Molecular Systems Biology·Jennifer A N Brophy, Christopher A Voigt
Apr 2, 2016·Science·Alec A K NielsenChristopher A Voigt
May 30, 2016·Current Opinion in Chemical Biology·Daniel Bojar, Martin Fussenegger
Jul 19, 2016·Molecular Cell·Jeong Wook LeeJames J Collins
Oct 19, 2016·Current Opinion in Microbiology·Robert W BradleyBaojun Wang
Oct 19, 2016·Current Opinion in Microbiology·Olivier BorkowskiTom Ellis
Mar 30, 2017·ACS Synthetic Biology·Yili QianDomitilla Del Vecchio
Apr 20, 2017·PloS One·Swati B CarrDouglas M Densmore

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Citations

Jul 17, 2020·Molecular Systems Biology·John T Sexton, Jeffrey J Tabor
Aug 20, 2020·Molecular Systems Biology·Yongjin ParkChristopher A Voigt
Aug 5, 2020·Nature Microbiology·Ye ChenChristopher A Voigt
Sep 16, 2020·Current Opinion in Biotechnology·César Carrasco-LópezJosé L Avalos
Nov 25, 2020·International Journal of Molecular Sciences·Minjeong KangSuhyung Cho
Mar 31, 2021·PloS One·Morgan MadecChristophe Lallement
May 23, 2021·Trends in Microbiology·Shengbo WuJianjun Qiao
Aug 14, 2020·ACS Synthetic Biology·Pedro FontanarrosaChris Myers
Jun 27, 2020·ACS Synthetic Biology·M Ali Al-RadhawiEduardo D Sontag
Oct 5, 2021·ACS Synthetic Biology·Lukas BuecherlChris J Myers
Sep 17, 2020·Cell Systems·Alexander P S Darlington, Declan G Bates

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Methods Mentioned

BETA
chip
PCR
flow cytometry

Software Mentioned

Cello
NOTgates
Verilog
TreeStar
Autodesk Fusion 360
Solver
Adobe Photoshop
MATLAB
FlowJo

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