Global architectures of biological networks

Prof. John Doyle, California Institute of Technology

This talk will sketch the insights about the fundamental nature of complex biological networks that can now be drawn from the convergence of three research themes. Molecular biology has provided a detailed description of the much of components of biological networks, and the organizational principles of these networks are becoming increasingly apparent. It is now clear that much of the complexity in biology is driven by its control systems, however poorly understood these remain. In addition, advanced technology is creating engineering examples of networks with complexity approaching that of biology. While the components are entirely different, there is striking convergence at the network level of the architecture and the role of protocols, layering, control, and feedback in structuring complex system modularity. Finally, there is a new mathematical framework for the study of complex networks that suggests that this apparent network-level evolutionary convergence both within biology and between biology and technology is not accidental, and follows necessarily from the requirements that both biology and technology be efficient and robust. Through combinations of evolution and natural selection or engineering design, such systems exhibit highly symbiotic interactions of extremely heterogeneous components to create functional hierarchies, with massive use of control and feedback throughout.

This talk will draw on concrete examples from systems biology to illustrate common themes and challenges in developing a scalable scientific theory and software infrastructure for complex networks. The larger aim is to build on mathematics of systems engineering to create a coherent and complete theoretical infrastructure proceeding from experimental data to modeling, analysis, inference, and with tight feedback to experimentation and modeling throughout. A crucial insight is that both technological design and evolution favor high robustness to uncertain environments and components, yet allows severe fragility to novel perturbations, and this "robust yet fragile" feature must be exploited explicitly in scalable theoretical and algorithmic approaches. This talk will focus on the discussing our new understanding of the intrinsic features of biological complexity in terms accessible to biologists, and with a minimum of mathematical details. The mathematical implications however are important, as a theoretical and software infrastructure that does not explicitly exploit the highly structured, evolved and/or designed, and "robust yet fragile" nature of such systems is hopelessly doomed to be overwhelmed by their sheer complexity.

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