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Global view of bionetwork dynamics:adaptive landscape

Journal of Genetics and Genomics 2009年第2期36卷 63-73页

作者： Ping Ao Department of Mechanical Engineering and Department of Physics University of Washington Seattle WA 98195 USA Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine of Ministry of Education Shanghai Jiao Tong University Shanghai 200240 China

Based on recent work, I will give a nontechnical brief review of a powerful quantitative concept in biology, adaptive landscape, ini- tially proposed by S. Wright over 70 years ago, reintroduced by one of the founders of molecular biology and by others in different bio- logical contexts, but apparently forgotten by modem biologists for many years. Nevertheless, this concept finds an increasingly important role in the development of systems biology and bionetwork dynamics modeling, from phage lambda genetic switch to endogenous net- work for cancer genesis and progression. It is an ideal quantification to describe the robustness and stability of bionetworks. Here, I will first introduce five landmark proposals in biology on this concept, to demonstrate an important common thread in theoretical biology. Then I will discuss a few recent results, focusing on the studies showing theoretical consistency of adaptive landscape. From the perspec- tive of a working scientist and of what is needed logically for a dynamical theory when confronting empirical data, the adaptive landscape is useful both metaphorically and quantitatively, and has captured an essential aspect of biological dynamical processes. Though at the theoretical level the adaptive landscape must exist and it can be used across hierarchical boundaries in biology, many associated issues are indeed vague in their initial formulations and their quantitative realizations are not easy, and are good research topics for quantitative biologists. I will discuss three types of open problems associated with the adaptive landscape in a broader perspective.

关键词： adaptive landscape stochastic dynamics, bionetworks systems biology

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From Phage lambda to human cancer： endogenous molecular-cellular network hypothesis

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Frontiers of Electrical and Electronic Engineering in China 2013年第1期8卷 32-49页

作者： Gaowei Wang Xiaomei Zhu Leroy Hood Ping Ao Ministry of Education Key Laboratory of Systems Biomedicine Shanghai Center for Systems Biomedicine Shanghai Jiao Tong University Shanghai 200240 China State Key Laboratory for Oncogenes and Related Genes Shanghai Cancer Institute Shanghai Jiao Tong University School of Medicine Shanghai 200032 China GenMath Corp. Seattle WA 98105 USA Institute for Systems Biology Seattle WA 98103 USA Department of Physics Shanghai Jiao Tong University Shanghai 200240 China

Experimental evidences and theoretical analyses have amply suggested that in cancer genesis and progression genetic information is very important but not the whole. Nevertheless, ＂cancer as a disease of the genome＂ is still currently the dominant doctrine. With such a background and based on the fundamental properties of biological systems, a new endogenous molecular-cellular network theory for cancer was recently proposed by us. Similar proposals were also made by others. The new theory attempts to incorporate both genetic and environmental effects into one single framework, with the possibility to give a quantitative and dynamical description. It is asserted that the complex regulatory machinery behind biological processes may be modeled by a nonlinear stochastic dynamical system similar to a noise perturbed Morse-Smale system. Both qualitative and quantitative descriptions may be obtained. The dynamical variables are specified by a set of endogenous molecular-cellular agents and the structure of the dynamical system by the interactions among those biological agents. Here we review this theory from a pedagogical angle which emphasizes the role of modularization, hierarchy and autonomous regulation. We discuss how the core set of assumptions is exemplified in detail in one of the simple, important and well studied model organisms, Phage lambda. With this concrete and quantitative example in hand, we show that the application of the hypothesized theory in human cancer, such as hepatocellular carcinoma （HCC）, is plausible, and that it may provide a set of new insights on understanding cancer genesis and progression, and on strategies for cancer prevention, cure, and care.

关键词： adaptive landscape Genetic Switch Intrinsic State Phage Lambda Regulatory Machinery

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