Systems Biology
Adam Arkin, University of California, Berkeley and E.O. Lawrence Berkeley National Laboratory

Over eons, evolution acts on organisms to hone their strategies for survival in an uncertain world. The ultimate substrate for evolution is the genome, the sequence of which implicitly encodes dynamic biochemical networks that process external signals into cellular actions. We are investigating approaches that link phylogenetic and comparative genomics analyses to physical chemical dynamics of cellular networks and evolutionary game theory to create a theory of the evolution and architecture of cellular networks. Ultimately we hope to divine principles of design in these systems which we can exploit to predict, control and design new behaviors in cellular networks. We have applied the fundamentals of this approach to understanding the evolution and dynamics of viral gene expression in HIV and bacterial stress response and signal transduction pathways particularly in Bacillus subtilis. We have demonstrated theoretically and experimentally the importance of molecular noise in the regulation of these networks and derived when, theoretically, such noise might be exploited to improve cellular fitness. We have used comparative functional genomic analysis to detect functional modules and to begin to detect selective pressures on different parts of network dynamics. We are beginning to use the derived principles for design of, for example, a tumor killing bacterium which must robustly and reliably sense its environment and change its strategies in its migration from serum to tissue to tumor. In this presentation we will show how tools of systems and synthetic biology are being brought together to create a new engineering discipline in cell biology.

1. Genome Biology 2006, 7:114 (doi:10.1186/gb-2006-7-8-114)
The electronic version of this article is the complete one and can be found online at


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