Abstract
Information processing is widely understood as the ability to change data in any meaningful manner. As such, this task is performed by natural systems as well as human-defined devices. The rational design of highly standardized electronic-based machines is a great source of inspiration for the synthetic biology community, which implements the same abstract concepts and theoretical functions with genetic technology in cells. For example, bacteria can be engineered to function as logic gates, adders or counters. However, the rules and concepts of electronic circuitry should not be literally translated into genetics. At least, not to the same extent in all cases. This issue needs to be addressed in order to establish a robust gene-based logic technology with its own specifications. This paper revise briefly the basics of genetic logic and, standing at the edge of biological and engineering sciences, tackles some recurrent misleading concepts and open questions
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References
Oldham P, Hall S, Burton G (2012) Synthetic biology: mapping the scientific landscape. PLoS One 7:e34368
Heinemann M, Panke S (2006) Synthetic biology-putting engineering into biology. Bioinformatics 22:2790–9
Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2(2006):0028
De Lorenzo V, Danchin A (2008) Synthetic biology: discovering new worlds and new words. EMBO reports 9:822–827
Benenson Y (2012) Biomolecular computing systems: principles, progress and potential. Nat Rev Genet 13:455–468
Wang B, Kitney RI, Joly N, Buck M (2011) Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology. Nat Commun 2:508
Hasty J, McMillen D, Collins JJ (2002) Engineered gene circuits. Nature 420:224–230
Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in escherichia coli. Nature 403:339–342
Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403:335–338
Purcell O, Savery NJ, Grierson CS, di Bernardo M (2010) A comparative analysis of synthetic genetic oscillators. J R Soc Interface 7:1503–24
Siuti P, Yazbek J, Lu TK (2013) Synthetic circuits integrating logic and memory in living cells. Nat Biotech 31:448–452
Bonnet J, Yin P, Ortiz ME, Subsoontorn P, Endy D (2013) Amplifying genetic logic gates. Science 340:599–603
Lou C, Liu X, Ni M, Huang Y, Huang Q et al (2010) Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch. Mol Syst Biol 6
Friedland AE, Lu TK, Wang X, Shi D, Church G et al (2009) Synthetic gene networks that count. Science 324:1199–1202
Brenner K, You L, Arnold FH (2008) Engineering microbial consortia: a new frontier in synthetic biology. Trends Biotechnol 26:483–9
Maca J, Posas F, Sol RV (2012) Distributed computation: the new wave of synthetic biology devices. Trends Biotechnol 30:342–349
Goñi-Moreno A, Redondo-Nieto M, Arroyo F, Castellanos J (2011) Biocircuit design through engineering bacterial logic gates. Nat Comput 10:119–127
Tamsir A, Tabor JJ, Ca Voigt (2011) Robust multicellular computing using genetically encoded NOR gates and chemical ’wires’. Nature 469:212–5
Regot S, Macia J, Conde N, Furukawa K, Kjellen J et al (2011) Distributed biological computation with multicellular engineered networks. Nature 469:207–211
Goñi-Moreno A, Amos M, de la Cruz F (2013) Multicellular computing using conjugation for wiring. PLoS ONE 8:e65986
Niazov T, Baron R, Katz E, Lioubashevski O, Willner I (2006) Concatenated logic gates using four coupled biocatalysts operating in series. Proc Natl Acad Sci 103:17160–17163
Strack G, Pita M, Ornatska M, Katz E (2008) Boolean logic gates that use enzymes as input signals. ChemBioChem 9:1260–1266
de Lorenzo V (2014) From the selfish gene to selfish metabolism: revisiting the central dogma. BioEssays
Goñi-Moreno A, Amos M (2012) Continuous computation in engineered gene circuits. Biosystems 109:52–56
Goñi-Moreno A, Amos M (2012) A reconfigurable nand/nor genetic logic gate. BMC Syst Biol 6:126
Daniel R, Rubens JR, Sarpeshkar R, Lu TK (2013) Synthetic analog computation in living cells. Nature 497:619–623
Kelly J, Rubin A, Davis J, Ajo-Franklin C, Cumbers J et al (2009) Measuring the activity of biobrick promoters using an in vivo reference standard. J Biol Eng 3:4
Garg A, Lohmueller JJ, Silver PA, Armel TZ (2012) Engineering synthetic tal effectors with orthogonal target sites. Nucl Acids Res 40:7584–7595
Blount BA, Weenink T, Vasylechko S, Ellis T (2012) Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology. PLoS ONE 7:e33279
Moon TS, Lou C, Tamsir A, Stanton BC, Voigt CA (2012) Genetic programs constructed from layered logic gates in single cells. Nature 491:249–253
Hooshangi S, Thiberge S, Weiss R (2005) Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc Natl Acad Sci USA 102:3581–3586
Dublanche Y, Michalodimitrakis K, Kümmerer N, Foglierini M, Serrano L (2006) Noise in transcription negative feedback loops: simulation and experimental analysis. Mol Syst Biol 2
Kaern M, Elston TC, Blake WJ, Collins JJ (2005) Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet 6:451–64
Raser JM, O’Shea EK (2004) Control of stochasticity in eukaryotic gene expression. Science 304:1811–1814
Eldar A, Elowitz MB (2010) Functional roles for noise in genetic circuits. Nature 467:167–173
Basu S, Gerchman Y, Collins CH, Arnold FH, Weiss R (2005) A synthetic multicellular system for programmed pattern formation. Nature 434:1130–1134
Goi-Moreno A, Amos M (2011) Model for a population-based microbial oscillator. Biosystems 105:286–294
Medema MH, van Raaphorst R, Takano E, Breitling R (2012) Computational tools for the synthetic design of biochemical pathways. Nat Rev Micro 10:191–202
Beal J, Lu T, Weiss R (2011) Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks. PLoS ONE 6:e22490
Beal J, Weiss R, Densmore D, Adler A, Appleton E et al (2012) An end-to-end workflow for engineering of biological networks from high-level specifications. ACS Syn Biol 1:317–331
Kratz A, Tomita M, Krishnan A (2008) GeNESiS: gene network evolution simulation software. BMC Bioinf 9:541
Crespo I, Krishna A, Le Bchec A, del Sol A (2013) Predicting missing expression values in gene regulatory networks using a discrete logic modeling optimization guided by network stable states. Nucl Acids Res 41:e8
Thomas S, Jin Y (2014) Reconstructing biological gene regulatory networks: where optimization meets big data. Evol Intel 7:29–47
Xu R, Wunsch D, Frank R (2007) Inference of genetic regulatory networks with recurrent neural network models using particle swarm optimization. IEEE/ACM Trans Computat Biol Bioinf 4:681–692
Lienert F, Lohmueller JJ, Garg A, Silver PA (2014) Synthetic biology in mammalian cells: next generation research tools and therapeutics. Nat Rev Mol Cell Biol 15:95–107
Auslander S, Auslander D, Muller M, Wieland M, Fussenegger M (2012) Programmable single-cell mammalian biocomputers. Nat Adv 123–127 (online publication)
Weber W, Fussenegger M (2012) Emerging biomedical applications of synthetic biology. Nat Rev Genet 13:21–35
Merulla D, Buffi N, Beggah S, Truffer F, Geiser M et al (2013) Bioreporters and biosensors for arsenic detection. Biotechnological solutions for a world-wide pollution problem. Curr Opin Biotechnol 24:534–541
Cho MK, Relman DA (2010) Synthetic life, ethics, national security, and public discourse. Science 329:38–39
Acknowledgments
This work was supported by Spanish MINECO (PIM2010 EEI-00609), project PSEUDOMONAS 2.0: Utilización de células vivas en biocatálisis industrial.
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Goñi-Moreno, A. On genetic logic circuits: forcing digital electronics standards?. Memetic Comp. 6, 149–155 (2014). https://doi.org/10.1007/s12293-014-0136-8
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DOI: https://doi.org/10.1007/s12293-014-0136-8