Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Reverse engineering intracellular biochemical networks

Although much is known about the molecular components of cellular signaling pathways, very little is known about how these multicomponent biochemical machineries process complex extracellular signals to generate a consolidated cellular response. A newly developed theoretical approach for reverse engineering network structure—analyzing how perturbations propagate in a network—can be combined with chemical perturbations and quantitative detection approaches to reveal the causal connections within protein networks in cells. This information indicates the dynamic capabilities of a network and thereby its potential function.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Network topology: biochemical reaction scheme versus causal connectivity.
Figure 2: Reverse engineering a network structure.
Figure 3: Enzyme–substrate imaging.

References

  1. Tyson, J.J., Chen, K.C. & Novak, B. Curr. Opin. Cell Biol. 15, 221–231 (2003).

    Article  CAS  Google Scholar 

  2. Kholodenko, B.N. Nat. Rev. Mol. Cell Biol. 7, 165–176 (2006).

    Article  CAS  Google Scholar 

  3. Kholodenko, B.N. et al. Proc. Natl. Acad. Sci. USA 99, 12841–12846 (2002).

    Article  CAS  Google Scholar 

  4. Sontag, E., Kiyatkin, A. & Kholodenko, B.N. Bioinformatics 20, 1877–1886 (2004).

    Article  CAS  Google Scholar 

  5. Santos, S.D., Verveer, P.J. & Bastiaens, P.I. Nat. Cell Biol. 9, 324–330 (2007).

    Article  CAS  Google Scholar 

  6. Hartwell, L.H., Hopfield, J.J., Leibler, S. & Murray, A.W. Nature 402, C47–C52 (1999).

    CAS  Google Scholar 

  7. Pei, Y. & Tuschl, T. Nat. Methods 3, 670–676 (2006).

    Article  CAS  Google Scholar 

  8. Karaman, M.W. et al. Nat. Biotechnol. 26, 127–132 (2008).

    Article  CAS  Google Scholar 

  9. Levitzki, A. & Mishani, E. Annu. Rev. Biochem. 75, 93–109 (2006).

    Article  CAS  Google Scholar 

  10. Knight, Z.A. & Shokat, K.M. Cell 128, 425–430 (2007).

    Article  CAS  Google Scholar 

  11. Bishop, A.C. et al. Nature 407, 395–401 (2000).

    Article  CAS  Google Scholar 

  12. Gregan, J. et al. Nat. Protoc. 2, 2996–3000 (2007).

    Article  CAS  Google Scholar 

  13. Banaszynski, L.A. & Wandless, T.J. Chem. Biol. 13, 11–21 (2006).

    Article  CAS  Google Scholar 

  14. Inoue, T., Heo, W.D., Grimley, J.S., Wandless, T.J. & Meyer, T. Nat. Methods 2, 415–418 (2005).

    Article  CAS  Google Scholar 

  15. Sachs, K., Perez, O., Pe'er, D., Lauffenburger, D.A. & Nolan, G.P. Science 308, 523–529 (2005).

    Article  CAS  Google Scholar 

  16. Olsen, J.V. et al. Cell 127, 635–648 (2006).

    Article  CAS  Google Scholar 

  17. Ong, S.E. & Mann, M. Nat. Chem. Biol. 1, 252–262 (2005).

    Article  CAS  Google Scholar 

  18. Elowitz, M.B., Levine, A.J., Siggia, E.D. & Swain, P.S. Science 297, 1183–1186 (2002).

    Article  CAS  Google Scholar 

  19. Wouters, F.S., Verveer, P.J. & Bastiaens, P.I. Trends Cell Biol. 11, 203–211 (2001).

    Article  CAS  Google Scholar 

  20. Bacia, K., Kim, S.A. & Schwille, P. Nat. Methods 3, 83–89 (2006).

    Article  CAS  Google Scholar 

  21. Maeder, C.I. et al. Nat. Cell Biol. 9, 1319–1326 (2007).

    Article  CAS  Google Scholar 

  22. Ting, A.Y., Kain, K.H., Klemke, R.L. & Tsien, R.Y. Proc. Natl. Acad. Sci. USA 98, 15003–15008 (2001).

    Article  CAS  Google Scholar 

  23. Zhang, J., Ma, Y., Taylor, S.S. & Tsien, R.Y. Proc. Natl. Acad. Sci. USA 98, 14997–15002 (2001).

    Article  CAS  Google Scholar 

  24. Yudushkin, I.A. et al. Science 315, 115–119 (2007).

    Article  CAS  Google Scholar 

  25. Melin, J. & Quake, S.R. Annu. Rev. Biophys. Biomol. Struct. 36, 213–231 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

E.Z. is supported by the European Union integrated project grant 'Interaction Proteome'.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zamir, E., Bastiaens, P. Reverse engineering intracellular biochemical networks. Nat Chem Biol 4, 643–647 (2008). https://doi.org/10.1038/nchembio1108-643

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio1108-643

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing