Hoteit, Imad (2011) Computational Simulation of Gene Regulatory Networks Implementing an Extendable Synchronous Single-Input Delay Flip-Flop and State Machine. Masters thesis, Concordia University.
Preview |
Text (application/pdf)
2MBHoteit_MASc_F2011.pdf - Accepted Version |
Abstract
We present a detailed and extendable design of the first synchronous single-input delay flip-flop implemented as a gene regulatory network in Escherichia coli (E. coli). The device, which we call the BioD, has one data input (trans-acting RNA), one clock input (far-red light) and an output that reports the state of the device using green fluorescent protein (GFP). The proposed design builds on Gardner’s toggle switch, to provide a more sophisticated device that can be synchronized with other devices within or without the same cell, and which requires only one data input. We provide a mathematical model of the system and simulation results. The results show that the device behaves in line with desired functionality. Further, we discuss the constraints of the design, which pertain to ranges of parameter values. The BioD is extended via the addition of an update function and input and output interfaces. The result is the BioFSM, which constitutes a synchronous and modular finite state machine, which uses an update function to change its state, stored in the BioD. The BioFSM uses its input and output interfaces for inter-cellular communications. This opens the door to the design of a circular cellular automata (the BioCell), which is envisioned as a number of communicating E. coli colonies, each made of clones of one BioFSM.
| Divisions: | Concordia University > Gina Cody School of Engineering and Computer Science > Electrical and Computer Engineering |
|---|---|
| Item Type: | Thesis (Masters) |
| Authors: | Hoteit, Imad |
| Institution: | Concordia University |
| Degree Name: | M.A. Sc. |
| Program: | Electrical and Computer Engineering |
| Date: | 4 October 2011 |
| Thesis Supervisor(s): | Kharma, Nawwaf |
| Keywords: | Escherichia coli, logic gates, synthetic biology, delay flip flop, finite state machine, cellular automata. |
| ID Code: | 35979 |
| Deposited By: | IMAD HOTEIT |
| Deposited On: | 17 Nov 2011 16:59 |
| Last Modified: | 18 Jan 2018 17:36 |
References:
Adleman,L.M. (1994). Molecular computation of solutions to combinatorial problems. Science 266, 1021-1024.Aksenov,S.V. (1999). Induction of the SOS Response in Ultraviolet-Irradiated Escherichia coli Analyzed by Dynamics of LexA, RecA and SulA Proteins. Journal of Biological Physics 25, 263-277.
Alon,U. (2006). An Introduction to Systems Biology Design Principles of Biological Circuits. (London: Chapman & Hall/CRC/Taylor & Francis).
Anderson,J.C., Clarke,E.J., Arkin,A.P., and Voigt,C.A. (2006). Environmentally controlled invasion of cancer cells by engineered bacteria. J. Mol. Biol. 355, 619-627.
Anderson,R.M., Zimprich,C.A., and Rust,L. (1999). A second operator is involved in Pseudomonas aeruginosa elastase (lasB) activation. J. Bacteriol. 181, 6264-6270.
Balagadde,F.K., Song,H., Ozaki,J., Collins,C.H., Barnet,M., Arnold,F.H., Quake,S.R., and You,L. (2008). A synthetic Escherichia coli predator-prey ecosystem. Mol. Syst. Biol. 4, 187.
Basu,S., Gerchman,Y., Collins,C.H., Arnold,F.H., and Weiss,R. (2005). A synthetic multicellular system for programmed pattern formation. Nature 434, 1130-1134.
Basu,S., Mehreja,R., Thiberge,S., Chen,M.T., and Weiss,R. (2004). Spatiotemporal control of gene expression with pulse-generating networks. Proc. Natl. Acad. Sci. U. S. A 101, 6355-6360.
Baumeister,R., Flache,P., Melefors,O., von,G.A., and Hillen,W. (1991). Lack of a 5' non-coding region in Tn1721 encoded tetR mRNA is associated with a low efficiency of translation and a short half-life in Escherichia coli. Nucleic Acids Res. 19, 4595-4600.
Bayer,T.S. and Smolke,C.D. (2005). Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat. Biotechnol. 23, 337-343.
Becskei,A., Seraphin,B., and Serrano,L. (2001). Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J. 20, 2528-2535.
Boyle,P.M. and Silver,P.A. (2009). Harnessing nature's toolbox: regulatory elements for synthetic biology. J. R. Soc. Interface 6 Suppl 4, S535-S546.
Camas,F.M., Blazquez,J., and Poyatos,J.F. (2006). Autogenous and nonautogenous control of response in a genetic network. Proc. Natl. Acad. Sci. U. S. A 103, 12718-12723.
Cao,Y., Gillespie,D.T., and Petzold,L.R. (2007). Adaptive explicit-implicit tau-leaping method with automatic tau selection. J. Chem. Phys. 126, 224101.
Cox,R.S.I., Surette,M.G., and Elowitz,M.B. (2007). Programming gene expression with combinatorial promoters. Mol. Syst. Biol. 3, 145.
de Jong,H. (2002). Modeling and simulation of genetic regulatory systems: a literature review. J. Comput. Biol. 9, 67-103.
de Jong,H., Ranquet,C., Ropers,D., Pinel,C., and Geiselmann,J. (2010). Experimental and computational validation of models of fluorescent and luminescent reporter genes in bacteria. BMC. Syst. Biol. 4, 55.
Drubin,D.A., Way,J.C., and Silver,P.A. (2007). Designing biological systems. Genes Dev. 21, 242-254.
Dueber,J.E., Yeh,B.J., Chak,K., and Lim,W.A. (2003). Reprogramming control of an allosteric signaling switch through modular recombination. Science 301, 1904-1908.
Elowitz,M.B. and Leibler,S. (2000). A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338.
Friedland,A.E., Lu,T.K., Wang,X., Shi,D., Church,G., and Collins,J.J. (2009). Synthetic gene networks that count. Science 324, 1199-1202.
Fuqua,C., Parsek,M.R., and Greenberg,E.P. (2001). Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu. Rev. Genet. 35, 439-468.
Gardner,T.S., Cantor,C.R., and Collins,J.J. (2000). Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339-342.
Gillespie,D.T. (1977). Exact stochastic simulation of coupled chemical reactions. The Journal of Physical Chemistry 81, 2340-2361.
Goryachev,A.B., Toh,D.J., and Lee,T. (2006). Systems analysis of a quorum sensing network: design constraints imposed by the functional requirements, network topology and kinetic constants. Biosystems 83, 178-187.
Ham,T.S., Lee,S.K., Keasling,J.D., and Arkin,A.P. (2006). A tightly regulated inducible expression system utilizing the fim inversion recombination switch. Biotechnol. Bioeng. 94, 1-4.
Ham,T.S., Lee,S.K., Keasling,J.D., and Arkin,A.P. (2008). Design and construction of a double inversion recombination switch for heritable sequential genetic memory. PLoS. One. 3, e2815.
Hartwell,L., Hood,L., Goldberg,M., Reynolds,A., and Silver,L. (2010). Genetics: From Genes to Genomes. McGraw-Hill Higher Education).
Haynes,K.A. and Silver,P.A. (2009). Eukaryotic systems broaden the scope of synthetic biology. J. Cell Biol. 187, 589-596.
Head,C.G., Tardy,A., and Kenney,L.J. (1998). Relative binding affinities of OmpR and OmpR-phosphate at the ompF and ompC regulatory sites. J. Mol. Biol. 281, 857-870.
Hindmarsh,A.C., Brown,P.N., Grant,K.E., Lee,S.L., Serban,R., Shumaker,D.E., and Woodward,C.S. (2005). SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers. ACM Trans. Math. Softw 31, 363-396.
Hong,M., Fitzgerald,M.X., Harper,S., Luo,C., Speicher,D.W., and Marmorstein,R. (2008). Structural basis for dimerization in DNA recognition by Gal4. Structure. 16, 1019-1026.
Isaacs,F.J., Dwyer,D.J., Ding,C., Pervouchine,D.D., Cantor,C.R., and Collins,J.J. (2004). Engineered riboregulators enable post-transcriptional control of gene expression. Nat. Biotechnol. 22, 841-847.
Janert,P.K. (2009). Gnuplot in Action. Manning Publications).
Kaps,P. and Rentrop,P. (1979). Generalized Runge-Kutta methods of order four with stepsize control for stiff ordinary differential equations. Numerische Mathematik 33, 55-68.
Knight, T., Endy, D., and Voight, C. The BioBricks Foundation. 2004.
Ref Type: Online Source
Knight, T. F., Jr. and Sussman, G. J. Cellular gate technology. UMC98: First International Conference On Unconventional Models Of Computation. [1], 257-272. 1-1-1998.
Ref Type: Conference Proceeding
Kobayashi,H., Kaern,M., Araki,M., Chung,K., Gardner,T.S., Cantor,C.R., and Collins,J.J. (2004). Programmable cells: interfacing natural and engineered gene networks. Proc. Natl. Acad. Sci. U. S. A 101, 8414-8419.
Kramer,B.P., Fischer,C., and Fussenegger,M. (2004). BioLogic gates enable logical transcription control in mammalian cells. Biotechnol. Bioeng. 87, 478-484.
Kuhner,F., Costa,L.T., Bisch,P.M., Thalhammer,S., Heckl,W.M., and Gaub,H.E. (2004). LexA-DNA bond strength by single molecule force spectroscopy. Biophys. J. 87, 2683-2690.
Levskaya,A., Chevalier,A.A., Tabor,J.J., Simpson,Z.B., Lavery,L.A., Levy,M., Davidson,E.A., Scouras,A., Ellington,A.D., Marcotte,E.M., and Voigt,C.A. (2005). Synthetic biology: engineering Escherichia coli to see light. Nature 438, 441-442.
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., and Ouyang,Q. (2010). Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch. Mol. Syst. Biol. 6, 350.
Medina,G., Juarez,K., Valderrama,B., and Soberon-Chavez,G. (2003). Mechanism of Pseudomonas aeruginosa RhlR transcriptional regulation of the rhlAB promoter. J. Bacteriol. 185, 5976-5983.
Mullock,B.M. and Luzio,J.P. (2005). Theory of Organelle Biogenesis: AHistorical Perspective. Springer US), pp. 1-18.
Olivier,B.G., Rohwer,J.M., and Hofmeyr,J.H. (2005). Modelling cellular systems with PySCeS. Bioinformatics 21, 560-561.
Orth,J.D., Thiele,I., and Palsson,B.O. (2010). What is flux balance analysis? Nat. Biotechnol. 28, 245-248.
Reinitz,J. and Vaisnys,J.R. (1990). Theoretical and experimental analysis of the phage lambda genetic switch implies missing levels of co-operativity. J. Theor. Biol. 145, 295-318.
Shih,M.C. and Gussin,G.N. (1984). Kinetic analysis of mutations affecting the cII activation site at the PRE promoter of bacteriophage lambda. Proc. Natl. Acad. Sci. U. S. A 81, 6432-6436.
Shrout,J.D. and Parsek,M.R. (2006). Quorum Sensing: Coordinating Group Behavior Through Intercellular Signals. In Molecular Paradigms of Infectious Disease, C.A.Nickerson and M.J.Schurr, eds. Springer US), pp. 404-437.
Steindler,L. and Venturi,V. (2007). Detection of quorum-sensing N-acyl homoserine lactone signal molecules by bacterial biosensors. FEMS Microbiol. Lett. 266, 1-9.
Stekel,D.J. and Jenkins,D.J. (2008). Strong negative self regulation of prokaryotic transcription factors increases the intrinsic noise of protein expression. BMC. Syst. Biol. 2, 6.
Stricker,J., Cookson,S., Bennett,M.R., Mather,W.H., Tsimring,L.S., and Hasty,J. (2008). A fast, robust and tunable synthetic gene oscillator. Nature 456, 516-519.
Sundararaj,S., Guo,A., Habibi-Nazhad,B., Rouani,M., Stothard,P., Ellison,M., and Wishart,D.S. (2004). The CyberCell Database (CCDB): a comprehensive, self-updating, relational database to coordinate and facilitate in silico modeling of Escherichia coli. Nucleic Acids Res. 32, D293-D295.
Swinburne,I.A., Miguez,D.G., Landgraf,D., and Silver,P.A. (2008). Intron length increases oscillatory periods of gene expression in animal cells. Genes Dev. 22, 2342-2346.
Tecon,R., Wells,M., and van der Meer,J.R. (2006). A new green fluorescent protein-based bacterial biosensor for analysing phenanthrene fluxes. Environ. Microbiol. 8, 697-708.
Tigges,M., Marquez-Lago,T.T., Stelling,J., and Fussenegger,M. (2009). A tunable synthetic mammalian oscillator. Nature 457, 309-312.
Vohradsky,J. (2001). Neural model of the genetic network. J. Biol. Chem. 276, 36168-36173.
Wang,Y.M., Tegenfeldt,J.O., Reisner,W., Riehn,R., Guan,X.J., Guo,L., Golding,I., Cox,E.C., Sturm,J., and Austin,R.H. (2005). Single-molecule studies of repressor-DNA interactions show long-range interactions. Proc. Natl. Acad. Sci. U. S. A 102, 9796-9801.
Weber,W., Stelling,J., Rimann,M., Keller,B., Daoud-El,B.M., Weber,C.C., Aubel,D., and Fussenegger,M. (2007). A synthetic time-delay circuit in mammalian cells and mice. Proc. Natl. Acad. Sci. U. S. A 104, 2643-2648.
Weiss, R., Homsy, G., and Nagpal, R. Programming biological cells. Eighth International Conference on Architectural Support for Programming Languages and Operating Systems. Wild and Crazy Ideas Session [8]. 1998.
Ref Type: Conference Proceeding
Wolfram,S. (2002). A New Kind Of Science.
Zhu,Y., Qin,L., Yoshida,T., and Inouye,M. (2000). Phosphatase activity of histidine kinase EnvZ without kinase catalytic domain. Proc. Natl. Acad. Sci. U. S. A 97, 7808-7813.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.
Repository Staff Only: item control page
Download Statistics
Download Statistics