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Elucidating the architecture and dynamics of large scale genetic regulatory networks of cells is an important goal in systems biology. We study the system level dynamical properties of the genetic network of Escherichia coli that regulates its metabolism, and show how its design leads to biologically useful cellular properties. Our study uses the database (Covert et al., Nature 2004) containing 583 genes and 96 external metabolites which describes not only the network connections but also the boolean rule at each gene node that controls the switching on or off of the gene as a function of its inputs. We have studied how the attractors of the boolean dynamical system constructed from this database depend on the initial condition of the genes and on various environmental conditions corresponding to buffered minimal media. We find that the system exhibits homeostasis in that its attractors, that turn out to be fixed points or low period cycles, are highly insensitive to initial conditions or perturbations of gene configurations for any given fixed environment. At the same time the attractors show a wide variation when external media are varied implying that the system mounts a highly flexible response to changed environmental conditions. The regulatory dynamics acts to enhance the cellular growth rate under changed media. Our study shows that the reconstructed genetic network regulating metabolism in {it E. coli} is hierarchical, modular, and largely acyclic, with environmental variables controlling the root of the hierarchy. This architecture makes the cell highly robust to perturbations of gene configurations as well as highly responsive to environmental changes. The twin properties of homeostasis and response flexibility are achieved by this dynamical system even though it is not close to the edge of chaos.
The genetic regulatory network (GRN) plays a key role in controlling the response of the cell to changes in the environment. Although the structure of GRNs has been the subject of many studies, their large scale structure in the light of feedbacks fr
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redu
The lactose operon in Escherichia coli was the first known gene regulatory network, and it is frequently used as a prototype for new modeling paradigms. Historically, many of these modeling frameworks use differential equations. More recently, Stigle
The set of regulatory interactions between genes, mediated by transcription factors, forms a species transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the
The analysis of stress response systems in microorganisms can reveal molecular strategies for regulatory control and adaptation. Here, we focus on the Cad module, a subsystem of E. colis response to acidic stress, which is conditionally activated at