Abstract
Synthetic gene circuits can be designed in an electronic fashion by displaying their basic components—Standard Biological Parts and Pools of molecules—on the computer screen and connecting them with hypothetical wires. This procedure, achieved by our add-on for the software ProMoT, was successfully applied to bacterial circuits. Recently, we have extended this design-methodology to eukaryotic cells. Here, highly complex components such as promoters and Pools of mRNA contain hundreds of species and reactions whose calculation demands a rule-based modeling approach. We showed how to build such complex modules via the joint employment of the software BioNetGen (rule-based modeling) and ProMoT (modularization). In this chapter, we illustrate how to utilize our computational tool for synthetic biology with the in silico implementation of a simple eukaryotic gene circuit that performs the logic AND operation.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Endy D (2005) Foundations for engineering biology. Nature 438:449–453
Marchisio MA, Colaiacovo M, Whitehead E, Stelling J (2013) Modular, rule-based modeling for the design of eukaryotic synthetic gene circuits. BMC Syst Biol 7:42
Mirschel S, Steinmetz K, Rempel M, Ginkel M, Gilles ED (2009) PROMOT: modular modeling for systems biology. Bioinformatics 25:687–689
Faeder JR, Blinov ML, Hlavacek WS (2009) Rule-based modeling of biochemical systems with BioNetGen. Methods Mol Biol 500:113–167
Ginkel M, Kremling A, Nutsch T, Rehner R, Gilles ED (2003) Modular modeling of cellular systems with ProMoT/Diva. Bioinformatics 19:1169–1176
Marchisio MA, Stelling J (2008) Computational design of synthetic gene circuits with composable parts. Bioinformatics 24:1903–1910
Marchisio MA, Stelling J (2009) Synthetic gene network computational design, In Proc. IEEE Int Symp Circuits Syst ISCAS 2009:309–312
Saez-Rodriguez J, Kremling A, Gilles ED (2005) Dissecting the puzzle of life: modularization of signal transduction networks. Comput Chem Eng 29:619–629
Lewin B (2000) Genes VII. Oxford University Press, New York
Marchisio MA, Stelling J (2013) Simplified computational design of synthetic gene digital circuits. In: Kulkarni V, Raman K, Stan G (eds) System theoretic and computational perspectives in systems and synthetic biology. Springer, New York
Marchisio MA, Stelling J (2011) Automatic design of digital synthetic gene circuits. PLoS Comput Biol 7:e1001083
Hucka M et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531
Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403:335–338
Massé E, Escorcia FE, Gottesman S (2003) Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev 17:2374–2383
Maul GG, Deaven L (1977) Quantitative determination of nuclear pore complexes in cycling cells with differing DNA content. J Cell Biol 73:748–760
Fujioka A, Terai K, Itoh RE, Aoki K, Nakamura T, Kuroda S, Nishida E, Matsuda M (2006) Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. J Biol Chem 281:8917–8926
Galdzicki M, Rodriguez C, Chandran D, Sauro HM, Gennari JH (2011) Standard biological parts knowledgebase. PLoS One 6:e17005
Hoops S, Sahle S, Gauges R, Lee C, Pahle J, Simus N, Singhal M, Xu L, Mendes P, Kummer U (2006) COPASI—a COmplex PAthway SImulator. Bioinformatics 22:3067–3074
Acknowledgment
This work was partially supported by the EU FP7 project ST-FLOW (contract 289326).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Marchisio, M.A. (2015). Modular Design of Synthetic Gene Circuits with Biological Parts and Pools. In: Marchisio, M. (eds) Computational Methods in Synthetic Biology. Methods in Molecular Biology, vol 1244. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1878-2_7
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1878-2_7
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-1877-5
Online ISBN: 978-1-4939-1878-2
eBook Packages: Springer Protocols