期刊论文详细信息
BMC Systems Biology
Synthesizing genetic sequential logic circuit with clock pulse generator
Chun-Liang Lin1  Chia-Hua Chuang1 
[1] Department of Electrical Engineering, National Chung Hsing University, Taichung 402, Taiwan, ROC
关键词: Optimization;    Logic circuit;    Clock signal;    Genetic oscillator;   
Others  :  866353
DOI  :  10.1186/1752-0509-8-63
 received in 2014-04-28, accepted in 2014-05-15,  发布年份 2014
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【 摘 要 】

Background

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future.

Results

This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency.

Conclusions

A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

【 授权许可】

   
2014 Chuang and Lin; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Andrianantoandro E, Basu S, Karig DK, Weiss R: Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2006, 2:1-14.
  • [2]Cuccato G, Gatta GD, di Bernardo D: Systems and synthetic biology: tackling genetic networks and complex diseases. Heredity 2009, 102:527-532.
  • [3]Khalil AS, Collins JJ: Synthetic biology: applications come of age. Nat Rev Genet 2010, 11:367-379.
  • [4]Ruder WC, Lu T, Collins JJ: Synthetic biology moving into the clinic. Science 2011, 333:1248-1252.
  • [5]Sprinzak D, Elowitz MB: Reconstruction of genetic circuits. Nature 2005, 438:443-448.
  • [6]Chen L, Wang R: Designing gene regulatory networks with specified functions. IEEE Trans Circuits Syst I Regul Pap 2006, 53(11):2444-2450.
  • [7]Ichinose N, Yada T, Gotoh O, Aihara K: Reconstruction of transcription-translation dynamics with a model of gene networks. J Theor Biol 2008, 255:378-386.
  • [8]Lu TK, Khalil AS, Collins JJ: Next-generation synthetic gene networks. Nat Biotechnol 2009, 27:1139-1150.
  • [9]Gardner TS, Cantor CR, Collins JJ: Construction of a genetic toggle switch in Escherichia coli. Nature 2000, 403:339-342.
  • [10]Elowitz MB, Leibler S: A synthetic oscillatory network of transcriptional regulators. Nature 2000, 403:335-338.
  • [11]Novak B, Tyson JJ: Design principle of biochemical oscillator. Nat Rev Mol Cell Biol 2008, 9:981-991.
  • [12]Purcell O, Savery NJ, Grierson CS, di Bernardo M: A comparative analysis of synthetic genetic oscillators. J R Soc Interface 2010, 7(52):1503-1524.
  • [13]O’Brien EL, Itallie EV, Bennett MR: Modeling synthetic gene oscillator. Math Biosci 2012, 236(1):1-15.
  • [14]Basu S, Mehreja R, Thiberge S, Chen MT, Weiss R: Spatiotemporal control of gene expression with pulse-generating networks. Proc Natl Acad Sci U S A 2004, 101(17):6355-6360.
  • [15]Ishihara S, Fujimoto K, Shibata T: Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripes. Genes Cells 2005, 10(11):1025-1038.
  • [16]Buchler NE, Gerland U, Hwa T: On schemes of combinatorial transcription logic. Proc Natl Acad Sci U S A 2003, 100(9):5136-5141.
  • [17]Weiss R, Basu S, Hooshangi S, Kalmbach A, Karig D, Mehreja R, Netravali I: Genetic circuit building blocks for cellular computation, communications, and signal processing. Nat Comput 2003, 2(1):47-84.
  • [18]Silva-Rocha R, de Lorenzo V: Mining logic gates in prokaryotic transcriptional regulation networks. FEBS Lett 2008, 582(8):1237-1244.
  • [19]Buchler NE, Gerland U, Hwa T: Nonlinear protein degradation and the function of genetic circuits. Proc Natl Acad Sci U S A 2005, 102(27):9559-9564.
  • [20]Anderson JC, Voigt CA, Arkin AP: Environmental signal integration by a modular AND gate. Mol Syst Biol 2007, 3(133):1-8.
  • [21]Tamsir A, Tabor JJ, Voigt CA: Robust multicellular computing using genetically encoded NOR gates and chemical 'wires’. Nature 2011, 469:212-215.
  • [22]Wang B, Kitney RI, Joly N, Buck M: Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology. Nat Commun 2011, 2:1-9.
  • [23]Hooshangi S, Thiberge S, Weiss R: Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc Natl Acad Sci U S A 2005, 102(102005):3581-3586.
  • [24]Terzer M, Jovanovic M, Choutko A, Nikolayeva O, Korn A, Brockhoff D, Zurcher F, Friedmann M, Schutz R, Zitzler E, Stelling J, Panke S: Design of a biological half adder. IET Syst Biol 2007, 1:53-58.
  • [25]Moskon M, Ciglic M, Zimic N, Mraz M: Toward in vivo digital synchronous sequential circuits. WSEAS Transactions on circuits and systems 2009, 8:301-310.
  • [26]Zabet NR, Hone ANW, Chu DF: Design principles of transcriptional logic circuits. In Artificial Life XII Proceedings of the Twelfth International Conference on the Synthesis and Simulation of Living Systems. Odense, Denmark: The MIT Press; 2010:186-193.
  • [27]Lou C, Liu X, Ni M, Huang Y, Huang Q, Huang L, Jiang L, Lu D, Wang M, Liu C, Chen D, Chen C, Chen X, Yang L, Ma H, Chen J, Ouyang Q: Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch. Mol Syst Biol 2010, 6(350):1-11.
  • [28]Hoteit I, Kharma N, Varin L: Computational simulation of a gene regulatory network implementing an extendable synchronous single-input delay flip-flop. BioSystems 2012, 109:57-71.
  • [29]Subsoontorn P, Endy D: Design and analysis of genetically encoded counter. Procedia Comput Sci 2012, 11:43-54.
  • [30]Chuang CH, Lin CL, Chang YC, Jennawasin T, Chen PK: Design of synthetic biological logic circuits based on evolutionary algorithm. IET Syst Biol 2013, 7(4):89-105.
  • [31]Westermark PO, Herzel H: Mechanism for 12Hr rhythm generation by the circadian clock. Cell Rep 2013, 3:1228-1238.
  • [32]Purcell O, di Bernardo M, Grierson CS, Savery NJ: A multi-functional synthetic gene network: a frequency multiplier, oscillator and switch. PLoS One 2011, 6(2):1-12.
  • [33]Chen BS, Wu CH: A systematic design method for robust synthetic biology to satisfy design specifications. BMC Syst Biol 2009, 3(66):1-18.
  • [34]Chen BS, Chang CH, Wang YC, Wu CH, Lee HC: Robust model matching design methodology for a stochastic synthetic gene network. Math Biosci 2011, 230:23-36.
  • [35]Chang YC, Lin CL, Jennawasin T: Design of synthetic genetic oscillators using evolutionary optimization. Evol Bioinform 2013, 9:137-150.
  • [36]Zhang W, Zou X: Synchronization ability of coupled cell-cycle oscillators in changing environments. BMC Syst Biol 2012, 6(S13):1-14.
  • [37]Chen BS, Hsu CY: Robust synchronization control scheme of a population of nonlinear stochastic synthetic genetic oscillators under intrinsic and extrinsic molecular noise via quorum sensing. BMC Syst Biol 2012, 6(136):1-15.
  • [38]Rodrigo G, Carrera J, Jaramillo A: Computational design of synthetic regulatory networks from a genetic library to characterize the designability of dynamical behaviors. Nucleic Acids Res 2011, 39(20):1-12.
  • [39]Lee YY, Hsu CY, Lin LJ, Chang CC, Cheng HC, Yeh TH, Hu RH, Lin C, Xie Z, Chen BS: Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries. BMC Syst Biol 2013, 7(109):1-11.
  • [40]Maini AK: Digital Electronics: Principles, Devices and Applications. England: Wiley; 2007.
  • [41]Su WW, Liu B, Lu WB, Xu NS, Du GC, Tan JL: Observer-based online compensation of inner filter effect in monitoring fluorescence of GFP-expressing plant cell cultures. Biotechnol Bioeng 2005, 91:213-226.
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