The Robustness/Sensitivity Paradox: An Essay on the Importance of Phase Separation

  • Alessandro GiulianiEmail author
Part of the History, Philosophy and Theory of the Life Sciences book series (HPTL, volume 23)


Considering biological systems at different levels of organization as complex networks in which nodes (genes, proteins, metabolites…) are each other connected by (co-expression, physical interactions) is a very natural way of reasoning. Network approach allows scientist to make sense of the intricacies of biological regulation and, for the same mathematical nature of graphs, to obtain a multilevel description linking single node and whole network topological features. This paradigm allows for the detection of a clear signature of robustness: the ability of a system to keep separate different scales of response to environmental stimuli. A case study on the immune system allows for an immediate appreciation of this point.


Self-organization Gene expression regulation Networks Systems biology Innate immunity 


  1. Censi, F., Bartolini, P., Giuliani, A., & Calcagnini, G. (2010). A systems biology strategy on differential gene expression data discloses some biological features of atrial fibrillation. PLoS One, 5(10), e13668.CrossRefGoogle Scholar
  2. Conti, F., Valerio, M. C., Zbilut, J. P., & Giuliani, A. (2007). Will systems biology offer new holistic paradigms to life sciences? Systems and Synthetic Biology, 1(4), 161–165.CrossRefGoogle Scholar
  3. Felli, N., Cianetti, L., Pelosi, E., Carè, A., Gong Liu, C., Calin, G. A., Peschle, C., Rossi, S., Marziali, G., & Giuliani, A. (2010). Hematopoietic differentiation: A coordinated dynamical process towards attractor stable states. BMC Systems Biology, 4, 85.CrossRefGoogle Scholar
  4. Giuliani, A., Filippi, S., & Bertolaso, M. (2014). Why network approach can promote a new way of thinking in biology. Frontiers in Genetics, 5(83), 1–9.Google Scholar
  5. Huang, S. (2009). Reprogramming cell fates: Reconciling rarity with robustness. BioEssays, 31, 546–560.CrossRefGoogle Scholar
  6. Kauffmann, S. A. (1993). The origins of order. Self-organization and selection in evolution. New York: Oxford University Press.Google Scholar
  7. Kauffmann, S. A., Peterson, C., Samuelsson, B., & Troein, C. (2003). Random Boolean network and the yeast transcription network. Proceedings of the National Academy of Sciences of the United States of America, 100, 14796–14799.CrossRefGoogle Scholar
  8. Lima de Faria, A. (1988). Evolution without selection. Form and function by autoevolution. Amsterdam: Elsevier.Google Scholar
  9. Nykter, M., Price, D. N., Aldana, M., Ramsey, S. A., Kauffmann, S. A., Hood, L. E., Yli-Harja, O., & Shmulevich, I. (2008). Gene expression dynamics in the macrophage exhibit criticality. Proceedings of the National Academy of Sciences of the United States of America, 105, 1897–1900.CrossRefGoogle Scholar
  10. Palumbo, M. C., Colosimo, A., Giuliani, A., & Farina, L. (2007). Essentiality is an emergent property of metabolic network wiring. FEBS Letters, 581(13), 2485–2489.CrossRefGoogle Scholar
  11. Raeymakers, L. (2002). Dynamics of boolean networks controlled by biologically meaningful functions. Journal of Theoretical Biology, 218, 331–341.CrossRefGoogle Scholar
  12. Tsuchiya, M., Piras, V., Choi, S., Akira, S., Tomita, M., Giuliani, A., & Selvarajoo, K. (2009a). Emergent genome-wide control in wildtype and genetically mutated lipopolysaccarides-stimulated macrophages. PLoS One, 4, e4905.CrossRefGoogle Scholar
  13. Tsuchiya, M., Selvarajoo, K., Piras, B., Tomita, M., & Giuliani, A. (2009b). Local and global responses in complex gene regulation networks. Physica A, 388, 738–1746.CrossRefGoogle Scholar
  14. Yehuda, R. (2002). Post-traumatic stress disorder. New England Journal of Medicine, 346(2), 108–114.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Environment and Health DepartmentIstituto Superiore di SanitàRomeItaly

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