Skip to main content

Understanding the Bacterial Stringent Response Using Reachability Analysis of Hybrid Systems

  • Conference paper

Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 2993))

Abstract

In this paper we model coupled genetic and metabolic networks as hybrid systems. The vector fields are multi – affine, i.e., have only product – type nonlinearities to accommodate chemical reactions, and are defined in rectangular invariants, whose facets correspond to changes in the behavior of a gene or enzyme. For such systems, we showed that reachability and safety verification problems can be formulated and solved (conservatively) in an elegant and computationally inexpensive way, based on the fact that multi-affine functions on rectangular regions of the space are determined at the vertices. Using these techniques, we study the stringent response system, which is the transition of bacterial organisms from growth phase to a metabolically suppressed phase when subjected to an environment with limited nutrients.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Glass, L.: Classification of biological networks by their qualitative dynamics. Journal of Theoretical Biology 54, 85–107 (1975)

    Article  Google Scholar 

  2. Mestl, T., Plathe, E., Omholt, S.W.: Periodic solutions in systems of piecewiselinear differential equations. Dynamics and stability of systems 10(2), 179–193 (1995)

    MATH  MathSciNet  Google Scholar 

  3. de Jong, H., Gouze, J.L., Hernandez, C., Page, M., Sari, T., Geiselmann, J.: Hybrid modeling and simulation of genetic regulatory networks: a qualitative approach. In: Hybrid Systems: Computation and Control (2003)

    Google Scholar 

  4. Kauffmann, S.A.: Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology 22, 437–467 (1969)

    Article  Google Scholar 

  5. Thomas, R.: Regulatory networks seen as asynchronous automata: a logical description. Journal of Theoretical Biology 153, 1–23 (1991)

    Article  Google Scholar 

  6. Kuipers, B.: Qualitative simulation. Artificial intelligence 29, 289–388 (1981)

    Article  MathSciNet  Google Scholar 

  7. Brutlag, D.L., Galper, A.R., Millis, D.H.: Knowledge-based simulation of dna metabolism: prediction of enzyme action. Computer Applications in the Biosciences 7(1), 9–19 (1991)

    Google Scholar 

  8. Kauffmann, S.A.: The origins of order: self-organization and selection in evolution. Oxford University Press, New York (1993)

    Google Scholar 

  9. Mjolsness, E., Sharp, D.H., Reinitz, J.: A connectionist model of development. Journal of Theoretical Biology 152, 429–453 (1991)

    Article  Google Scholar 

  10. Gillespie, D.T.: Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 81, 2340–2361 (1977)

    Article  Google Scholar 

  11. McAdams, H.M., Arkin, A.: Stochastic mechanisms in gene expression. Proceedings of the National Academy of Science of the USA 94, 814–819 (1997)

    Article  Google Scholar 

  12. Gillespie, D.T.: Fluctuation and Dissipation in Brownian Motion. Am. J. Phys. 61, 1077–1083 (1993)

    Google Scholar 

  13. Alur, R., Henzinger, T.A., Sontag, E.D. (eds.): HS 1995. LNCS, vol. 1066. Springer, Heidelberg (1996)

    Google Scholar 

  14. Henzinger, T., Sastry, S. (eds.): HSCC 1998. LNCS, vol. 1386. Springer, Heidelberg (1998)

    MATH  Google Scholar 

  15. Vaandrager, F., van Schuppen, J. (eds.): Hybrid Systems: Computation and Control. LNCS, vol. 1569. Springer, Heidelberg (1999)

    MATH  Google Scholar 

  16. Lynch, N., Krogh, B.H. (eds.): HSCC 2000. LNCS, vol. 1790. Springer, Heidelberg (2000)

    MATH  Google Scholar 

  17. Tomlin, C., Ghosh, R.: Lateral inhibition through delta-notch signaling: A piecewise affine hybrid model. In: Di Benedetto, M.D., Sangiovanni-Vincentelli, A.L. (eds.) HSCC 2001. LNCS, vol. 2034, Springer, Heidelberg (2001)

    Google Scholar 

  18. Alur, R., Belta, C., Ivancic, F., Kumar, V., Rubin, H., Schug, J., Sokolsky, O., Webb, J.: Visual programming for modeling and simulation of bioregulatory networks. In: International Conference on High Performance Computing, Bangalore, India (2002)

    Google Scholar 

  19. Belta, C., Habets, L., Kumar, V.: Control of multi-affine systems on rectangles with applications to hybrid biomolecular networks. In: 41st IEEE Conference on Decision and Control, Los Angeles, NV (2002)

    Google Scholar 

  20. Belta, C., Schug, J., Dang, T., Kumar, V., Pappas, G.J., Rubin, H., Dunlap, P.V.: Stability and reachability analysis of a hybrid model of luminescence in the marine bacterium vibrio fischeri. In: 40th IEEE Conference on Decision and Control, Orlando, FL (2001)

    Google Scholar 

  21. Alur, R., Belta, C., Kumar, V., Mintz, M., Pappas, G.J., Rubin, H., Schug, J.: Modeling and analyzing biomolecular networks. Computing in Science and Engineering, 20–30 (January/February 2002)

    Google Scholar 

  22. Alur, R., Belta, C., Ivancic, F., Kumar, V., Mintz, M., Pappas, G., Schug, J.: Hybrid modelling and simulation of biomolecular networks. In: Di Benedetto, M.D., Sangiovanni-Vincentelli, A.L. (eds.) HSCC 2001. LNCS, vol. 2034, pp. 19–32. Springer, Heidelberg (2001)

    Chapter  Google Scholar 

  23. Primm, T.P., Andersen, S.J., Mizrahi, V., Avarbock, D., Rubin, H., Barry III, C.E.: The stringent response of Mycobacterium tuberculosis is required for long-term survival. J. Bacteriol. 182(17), 4889–4898 (2000)

    Article  Google Scholar 

  24. Gourse, R.L., Gaal, T., Bartlett, M.S., Appleman, J.A., Ross, W.: rrna transcription and growth rate-dependent regulation of ribosome synthesis. Escherichia coli. Annu. Rev. Microbiol. 50, 645–677 (1996)

    Google Scholar 

  25. Avarbock, D., Salem, J., Li, L., Wang, Z., Rubin, H.: Cloning and characterization of a bifunctional RelA/SpoT homologue from Mycobacterium tuberculosis. Gene 233, 261–269 (1999)

    Article  Google Scholar 

  26. Avarbock, D., Avarbock, A., Rubin, H.: Differential regulation of opposing activities by the amino-acylation state of a tRNA · Ribosome · mRNA · Rel Mtb complex. Biochemistry 39, 11640–11648 (2000)

    Article  Google Scholar 

  27. Barker, M.M., Gaal, T., Josaitis, C.A., Gourse, R.L.: Mechanism of regulation of transcription initiation by ppgpp. i. effects of (p)ppGpp on transcription initiation in vivo and in vitro. J. Mol. Biol. 305(4), 673–688 (2001)

    Article  Google Scholar 

  28. Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A., Duncan, K.: Evaluation of a nutrient starvation model of mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43(3), 717–731 (2002)

    Article  Google Scholar 

  29. Belta, C., Finin, P., Halász, Á., Imieliǹski, M., Kumar, V., Rubin, H.: Stringent Response in Mycobacterium tuberculosis. A technical document is available upon request (in preparation)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Belta, C. et al. (2004). Understanding the Bacterial Stringent Response Using Reachability Analysis of Hybrid Systems. In: Alur, R., Pappas, G.J. (eds) Hybrid Systems: Computation and Control. HSCC 2004. Lecture Notes in Computer Science, vol 2993. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-24743-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-24743-2_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-21259-1

  • Online ISBN: 978-3-540-24743-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics