Stochastic Game Theory Approach to Robust Synthetic Gene Network Design

The development of foundational technologies such as de novo DNA synthesis, milestone experiments such as the computational re-design of enzymes, the opportunity to widely recombine zinc fingers to re-program DNA-binding site specificity and the availability of well-studied model regulatory system for the design of engineering-inspired molecular devices provide a very powerful knowledge and technology basis for building novel biological entities (Heinemann and Panke, 2006). Synthetic biology is to engineer artificial biological systems to investigate natural biological phenomena and for a variety of applications. Synthetic biology will revolutionize how we conceptualize and approach the engineering of biological systems. The vision and applications of this emerging field will influence many other scientific and engineering disciplines, as well as affect various aspects of daily life and society (Andrianantoandro et al., 2006). Synthetic biology builds living machines from the off-the-shelf chemical ingredients, utilizing many of the same strategies that electrical engineers employ to make computer chips (Tucker & Zilinskas, 2006). The main goal of the nascent field of synthetic biology is to design and construct biological systems with the desired behavior (Alon, 2003; Alon, 2007; Andrianantoandro et al., 2006; Church, 2005; Endy, 2005; Hasty et al., 2002; Heinemann & Panke, 2006; Kobayashi et al., 2004; Pleiss, 2006; Tucker & Zilinskas, 2006). By a set of powerful techniques for the automated synthesis of DNA molecules and their assembly into genes and microbial genomes, synthetic biology envisions the redesign of natural biological systems for greater efficiency as well as the construction of functional “genetic circuit” and metabolic pathways for practical purposes (Andrianantoandro, et al., 2006; Ferber, 2004; Forster & Church, 2007; Gardner, et al., 2000; Heinemann & Panke, 2006; Isaacs, et al., 2006; Maeda & Sano, 2006; Tucker & Parker, 2000). Synthetic biology is foreseen to have important applications in biotechnology and medicine (Andrianantoandro et al., 2006). Though the engineering of networks of inter-regulating genes, so-called synthetic gene networks, has demonstrated the feasibility of synthetic biology (Gardner et al., 2000), the design of gene networks is still a difficult problem and most of the newly designed gene networks cannot work properly. These design failures are mainly due to intrinsic perturbations such as gene expression noises, splicing, mutation, uncertain initial states and disturbances such as changing extra-cellular environments, and interactions with cellular context. Therefore, how to design a robust synthetic gene network, which could tolerate uncertain initial conditions, attenuate the effect of all disturbances and function properly on