Efficiency, robustness, and stochasticity of gene regulatory networks in systems biology: λ switch as a working example

Abstract

Phage λ is one of the most studied biological models in modern molecular biology. Over the past 50 years, quantitative experimental knowledge on this biological model has been accumulated at all levels: physics, chemistry, genomics, proteomics, functions, and more. All of its components are known in great detail. The theoretical task has been to integrate its components to make the organism work quantitatively and in a harmonic manner. This tests our biological understanding, and would lay a solid foundation for further explorations and applications, which is an obvious goal of systems biology. One of the outstanding challenges in doing this has been the so-called stability puzzle of the λ switch; the biologically observed robustness and the difficulty in mathematical reconstruction based on known experimental values. In this chapter, we review the recent theoretical and experimental efforts on tackling this problem. An emphasis is put on the minimum quantitative modeling, where a successful numerical agreement between experiments and modeling has been achieved. A novel method, tentatively named stochastic dynamical structure analysis, emerged from such study, and it is also discussed within a broad modeling perspective. © 2007 Humana Press Inc.