Using a quantitative blueprint to reprogram the dynamics of the flagella gene network.
Detailed understanding and control of biological networks will require a level of description similar to that of electronic engineering blueprints. Currently, however, even the best-studied systems are usually described using qualitative arrow diagrams. A quantitative blueprint requires in vivo measurements of (1) the relative strength of the interactions (numbers on the arrows) and (2) the functions that integrate multiple inputs. Here, we address this using a well-studied system, the flagella biosynthesis transcription network in Escherichia coli. We use theory and high-resolution experiments to obtain a quantitative blueprint with (1) numbers on the arrows, finding different hierarchies of activation coefficients for the two regulators, FlhDC and FliA; and (2) cis-regulatory input functions, which summate the input from the two regulators (SUM gates). We then demonstrate experimentally how this blueprint can be used to reprogram temporal expression patterns in this system, using controlled expression of the regulators or point mutations in their binding sites. The present approach can be used to define blueprints of other gene networks and to quantitatively reprogram their dynamics.
Kalir
Shiraz
S
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel 76100.
Alon
Uri
U
D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005407:Flagella / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics; D016680:Genome, Bacterial; D017711:Nonlinear Dynamics; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C064971:FliA protein, Bacteria; D012808:Sigma Factor; D015534:Trans-Activators; C090553:flhD protein, E coli