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Mathematical modelling of nonlinear dynamics generated from modular interconnections in cellular SOS response system

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Abstract

Nonlinear dynamics in synthetic biology systems, generated as a consequence of interconnections between biological modules, poses challenges to the objective of engineering biological systems with predictable characteristics. Mathematical models, that often provide accurate descriptions of the biological modules in isolation, fail to capture such nonlinearities that arise in the interconnected modules. Without the modelling and quantification of these nonlinearities, systems biology models cannot be predictable or reliable. Hence it become a key area of focus of systems and synthetic biologists. To this end, we analyse the nonlinearities in the SOS response system, a prime cellular network in bacterial cells that functions to repair the DNA damage. It is shown that the dynamics of the modules in the SOS response system differ in isolation and in integration, and substantial variation is observed when more modules are connected. The interdependence among major modules is quantified, which imparts whether the integrated dynamics is an attenuation or amplification of the isolated dynamics. From a synthetic biology perspective, our study contributes to the effective engineering of biological devices from the integration of biological modules in a bottom-up fashion. Meanwhile, it also complements the investigations on the DNA damage repairing mechanism in living cells.

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References

  1. Elowitz, M.B., Leibler, S.: A synthetic oscillatory network of transcriptional regulators. Nature 403(6767), 335 (2000)

    Article  Google Scholar 

  2. Gardner, T.S., Cantor, C.R., Collins, J.J.: Construction of a genetic toggle switch in Escherichia coli. Nature 403(6767), 339 (2000)

    Article  Google Scholar 

  3. Bayer, T.S., Smolke, C.D.: Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat. Biotechnol. 23(3), 337 (2005)

    Article  Google Scholar 

  4. 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., Voigt, C.A.: Synthetic biology: engineering Escherichia coli to see light. Nature 434(7067), 441 (2005)

    Article  Google Scholar 

  5. Ro, D.K., Paradise, E.M., Ouellet, M., Fisher, K.J., Newman, K.L., Ndungu, J.M., Ho, K.A., Eachus, R.A., Ham, T.S., Kirby, J., Chang, M.C.Y., Withers, S.T., Shiba, Y., Sarpong, R., Keasling, J.D.: Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440(7086), 940 (2006)

    Article  Google Scholar 

  6. Del Vecchio, D., Ninfa, A.J., Sontag, E.D.: Modular cell biology: retroactivity and insulation. Mol. Syst. Biol. 4(1), 161 (2008)

    Google Scholar 

  7. Pantoja-Hernández, L., Martínez-García, J.C.: Retroactivity in the context of modularly structured biomolecular systems. Front. Bioeng. Biotechnol. 3, 85 (2015)

    Article  Google Scholar 

  8. Sauro, H.M.: The computational versatility of proteomic signaling networks. Curr. Proteom. 1(1), 67 (2004)

    Article  Google Scholar 

  9. Sauroa, H.M., Kholodenkoc, B.N.: Quantitative analysis of signaling networks. Prog. Biophys. Mol. Biol. 86(1), 5 (2004)

    Article  Google Scholar 

  10. Sauro, H.M., Ingalls, B.: MAPK Cascades as Feedback Amplifiers. ArXiv e-prints (2007)

  11. Syntheticbiology.org. http://syntheticbiology.org/FAQ.html. Accessed 3 October 2012

  12. Kreuzer, K.N.: DNA damage responses in prokaryotes: regulating gene expression, modulating growth patterns, and manipulating replication forks. Cold Spring Harb. Perspect. Biol. 5(11), a012674 (2013)

    Article  Google Scholar 

  13. Michel, B.: After 30 years of study, the bacterial SOS response still surprises us. PLoS Biol. 3(7), e255 (2005)

    Article  Google Scholar 

  14. François, P., Hakim, V.: Core genetic module: the mixed feedback loop. Phys. Rev. E Stat. Nonlinear Soft Matter Phys. 72(3), 031908 (2005)

    Article  MathSciNet  Google Scholar 

  15. Patel, M., Jiang, Q., Woodgate, R., Cox, M.M., Goodman, M.F.: A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V. Crit. Rev. Biochem. Mol. Biol. 45(3), 171 (2010)

    Article  Google Scholar 

  16. Witkin, E.M.: Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol. Rev. 40(4), 869 (1976)

    Google Scholar 

  17. Prescott, T.P., Lang, M., Papachristodoulou, A.: Quantification of interactions between dynamic cellular network functionalities by cascaded layering. PLoS Comput. Biol. 11(5), e1004235 (2015)

    Article  Google Scholar 

  18. Orth, J.D., Thiele, I., Palsson, B.ø: What is flux balance analysis? Nat. Biotechnol. 28(3), 245248 (2010)

    Article  Google Scholar 

  19. Hucka, M.: The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19(4), 524 (2003)

    Article  Google Scholar 

  20. Le Novère, N., Bornstein, B., Broicher, A., Courtot, M., Donizelli, M., Dharuri, H., Li, L., Sauro, H., Schilstra, M., Shapiro, B., Snoep, J.L., Hucka, M.: BioModels database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucleic Acids Res. 34(suppl1), D689 (2006)

    Article  Google Scholar 

  21. Bhaskaran, S., Nair, A.S.: Dynamical impact of autoregulation in SOS response system. In: Proceedings of 2016 NextGen Genomics, Biology, Bioinformatics and Technologies Conference, p. 137 (2016)

  22. Janion, C.: Inducible SOS response system of DNA repair and mutagenesis in Escherichia coli. Int. J. Biol. Sci. 4(6), 338 (2008)

    Article  Google Scholar 

  23. Friedman, N., Vardi, S., Ronen, M., Stavans, J.: Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria. PLoS Biol. 3(7), e238 (2005)

    Article  Google Scholar 

  24. Stavans, J.: The SOS response of bacteria to DNA damage. In: Dynamics of Complex Interconnected Systems: Networks and Bioprocesses. NATO Science Series II (Mathematics, Physics and Chemistry), vol. 232, pp. 39–47 (2006)

  25. Erental, A., Kalderon, Z., Saada, A., Smith, Y., Engelberg-Kulka, H.: Apoptosis-like death, an extreme SOS response in Escherichia coli. MBio 5(4), e01426 (2014)

    Article  Google Scholar 

  26. Cirz, R.T., Chin, J.K., Andes, D.R., de Crècy-Lagard, V., Craig, W.A., Romesberg, F.E.: Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol. 3(6), e176 (2005)

    Article  Google Scholar 

  27. N.L.M.C. at New York University School of Medicine. Factor preserves DNA integrity in bacteria despite assault from antibiotics: adjusting DNA repair may yield future solutions for antibiotic resistance and degenerative diseases. www.sciencedaily.com/releases/2016/05/160519144529.htm (2016)

  28. Jackson, S.P., Bartek, J.: The DNA-damage response in human biology and disease. Nature 461(7267), 1071 (2009)

    Article  Google Scholar 

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Acknowledgements

This work was funded by Kerala State Council for Science, Technology and Environment (KSCSTE) (Grant Number No. 124/2015/KSCSTE), Government of Kerala, India. We would also like to acknowledge the facilities provided by the Centre for Excellence in Ayur-Informatics Computer Aided Drug Design (Ai-CADD), University of Kerala.

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Correspondence to Silpa Bhaskaran.

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Bhaskaran, S., Nair, A.S. Mathematical modelling of nonlinear dynamics generated from modular interconnections in cellular SOS response system. Nonlinear Dyn 93, 643–652 (2018). https://doi.org/10.1007/s11071-018-4215-0

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