Synthesis of control unit for future biocomputer

BackgroundSynthesis of a variety of biological circuits for specific functional purposes has made a tremendous progress in recent years. The ultimate goal of combining molecular biology and engineering is to realize a functional biocomputer. To address this challenge, all previous efforts work toward building up the bio-computer as the ultimate goal. To this aim, there should be a key module, named control unit (CU), to direct a serious of logic or arithmetic operations within the processor.MethodsThis research task develops a bio-CU to work with a bio-ALU, which is realized from the combination of previously developed genetic logic gates to fulfill the kernel function of CPU as those done in the silicon computer.ResultsA possible framework of the bio-CPU has demonstrated how to connect a bio-CU with a bio-ALU to conduct a fetch-decode-execute cycle of a macro instruction. It presents not only capability of 4-bit full adder but coordination of related modules in biocomputer.ConclusionsWe have demonstrated computer simulation for applications of the genetic circuits in biocomputer construction. It’s expected to inspire follow-up study to synthesize potential configurations of the future biocomputer.

[1]  Chun-Liang Lin,et al.  A Novel Synthesizing Genetic Logic Circuit: Frequency Multiplier , 2014, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[2]  Rafael Silva-Rocha,et al.  Mining logic gates in prokaryotic transcriptional regulation networks , 2008, FEBS letters.

[3]  Eckart Zitzler,et al.  Design of a biological half adder , 2007 .

[4]  I. Blomfield.  The regulation of pap and type 1 fimbriation in Escherichia coli. , 2001, Advances in microbial physiology.

[5]  Christopher A. Voigt,et al.  Genetic circuit design automation , 2016, Science.

[6]  Marian Gheorghe,et al.  Design and Analysis of Genetically Constructed Logic Gates , 2015 .

[7]  Mario Lauria,et al.  Building blocks of a biochemical CPU based on DNA transcription logic , 2004 .

[8]  Richard I. Kitney,et al.  Layering genetic circuits to build a single cell, bacterial half adder , 2015, BMC Biology.

[9]  Chun-Liang Lin,et al.  Synthesising gene clock with toggle switch and oscillator. , 2015, IET systems biology.

[10]  M. Elowitz,et al.  Programming gene expression with combinatorial promoters , 2007, Molecular systems biology.

[11]  Maung Nyan Win,et al.  Raw Data, Win MN, Smolke CD. 2008. Higher-order cellular information processing with synthetic RNA devices. Science. 322: 456-60. DOI: 10.1126/science.1160311 , 2009 .

[12]  Tae J. Lee,et al.  Engineering Gene Circuits: Foundations and Applications , 2006 .

[13]  R. Weiss,et al.  Multi-input Rnai-based Logic Circuit for Identification of Specific , 2022 .

[14]  Chun-Liang Lin,et al.  Implementation of a genetic logic circuit: bio-register , 2015, Systems and Synthetic Biology.

[15]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[16]  M. Bennett,et al.  A fast, robust, and tunable synthetic gene oscillator , 2008, Nature.

[17]  Bo Liu,et al.  Observer-based online compensation of inner filter effect in monitoring fluorescence of GFP-expressing plant cell cultures. , 2005, Biotechnology and bioengineering.

[18]  G. Church,et al.  Next-Generation Digital Information Storage in DNA , 2012, Science.

[19]  Chun-Liang Lin,et al.  Synthesis of Genetic Clock with Combinational Biologic Circuits , 2015, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[20]  Chun-Liang Lin,et al.  Toward theoretical synthesis of biocomputer. , 2017, IET systems biology.

[21]  Chun-Liang Lin,et al.  Synthesizing genetic sequential logic circuit with clock pulse generator , 2014, BMC Systems Biology.

[22]  Ewan Birney,et al.  Towards practical, high-capacity, low-maintenance information storage in synthesized DNA , 2013, Nature.

[23]  Jörg Stelling,et al.  Automatic Design of Digital Synthetic Gene Circuits , 2011, PLoS Comput. Biol..

[24]  Bor-Sen Chen,et al.  GA-based Design Algorithms for the Robust Synthetic Genetic Oscillators with Prescribed Amplitude, Period and Phase , 2010, Gene regulation and systems biology.

[25]  Christopher A. Voigt,et al.  Environmental signal integration by a modular AND gate , 2007, Molecular systems biology.

[26]  M. Win,et al.  Higher-Order Cellular Information Processing with Synthetic RNA Devices , 2008, Science.

[27]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[28]  Takafumi Miyamoto,et al.  Synthesizing biomolecule-based Boolean logic gates. , 2013, ACS synthetic biology.

[29]  Baojun Wang,et al.  Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology , 2011, Nature communications.

[30]  Jie Chao,et al.  Structural DNA nanotechnology for intelligent drug delivery. , 2014, Small.

[31]  Tom F. A. de Greef,et al.  Antibody-controlled actuation of DNA-based molecular circuits , 2017, Nature Communications.

[32]  Chun-Liang Lin,et al.  Synthesising periodic triggering signals with genetic oscillators. , 2014, IET systems biology.

[33]  Christopher A. Voigt,et al.  Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ , 2011, Nature.

[34]  Ron Weiss,et al.  The Device Physics of Cellular Logic Gates , 2002 .

[35]  Nicolas E. Buchler,et al.  On schemes of combinatorial transcription logic , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Ashish Lamaniya.  Design of Full Adder and Full Subtractor using DNA Computing , 2014 .

[37]  Reid C. Johnson.  Bacterial Site-Specific DNA Inversion Systems , 2002 .

[38]  Chun-Liang Lin,et al.  Design of Synthetic Genetic Oscillators Using Evolutionary Optimization , 2013, Evolutionary bioinformatics online.

[39]  Nicolas E. Buchler,et al.  Nonlinear protein degradation and the function of genetic circuits. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Chun-Liang Lin,et al.  Design of synthetic biological logic circuits based on evolutionary algorithm. , 2013, IET systems biology.