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Complex systems and biology Biological systems • • • are composed of large numbers of functionally diverse elements, these elements interact selectively and nonlinearly, they have a function that they need to perform. The interactions between elements form a network. Understanding the dynamical behavior of these systems necessitates the understanding of their interconnections. An abstract representation of interaction networks and theoretical modeling can give general insights into system-level behavior. Gene expression is controlled by gene regulatory networks Network of the Drosophila segment polarity genes mRNA PROTEIN PROT COMPL repression translation, activation, modification cell neighbor cell R. Albert, H. G. Othmer, Journ. Theor. Biol. 223, 1 (2003) Cells respond to their environment by using signal transduction networks E. coli attractor receptor motor flagella tumbles swims Abstract representation of the bacterial chemotaxis signal transduction network R. Albert, Y-W Chiu, H. G. Othmer, submitted Signal transduction in plant guard cells CO2 Stomatal closure Light Light + ABA – ABA H2O Thanks to Sally Assmann, PSU Thanks to Song Li, PSU Modeling and experiments It is extremely important that models of biological networks are based on a synthesis of experimental knowledge about the system. Input: components; states of components, interactions Hypotheses: kinetics. Validation: capture known behavior. Explore: study cases that are not accessible experimentally change parameters, change assumptions Give predictions, gain insights Overall goal: identify common properties of biological networks dynamical: high amplification, robustness, adaptability, topological: redundancy, modularity, conserved regulatory motifs Topology of the yeast protein interaction network The heterogeneous organization is a common feature of numerous biological and non-biological networks. This implies robustness to random mutations, but vulnerability to mutations in highly-connected proteins. R. Albert, H. Jeong, A.-L. Barabási, Nature 406, 378 (2000) H. Jeong, S.P. Mason, A.-L. Barabasi, Z.N. Oltvai, Nature 411, 41-42 (2001) Identifying general themes in biological networks Can we identify subsets of the network that have well defined roles? • • Two antagonistic activating clusters… that enforce each other in neighboring cells • A regulatory source that maintains asymmetry. Regulatory motifs Flip-flop Negative feedback loop