Sensitivity of OR in Phage λ

Abstract

We investigate the sensitivity of the right operator in bacteriophage lambda. In particular, the system is probed in the three different regulatory protein concentration-regimes: 1), lysogen (CI dominates); 2), during induction (CI and Cro at comparable concentrations); and 3), after induction (Cro dominates). Systematic perturbations of the protein-operator binding energies show in a lysogen that the activity (production rate) at promoter PRM is robust to variations, in contrast to PR, where the sensitivity is high. Both promoters, however, show large sensitivity in regimes 2 and 3. In all regimes we identify several suppressors, meaning that for a given large perturbation (+/-2 kcal/mol) of one binding energy, there exist compensating perturbation(s) that restore the wild-type activity.

Bifurcation Analysis for Phage Lambda with Binding Energy Uncertainty

“…Since Δ 12 and Δ 3 have the minimum bistable ranges, the uncertainties of these two parameters are more likely to lead to the loss of bistable behavior. This is consistent with the conclusion by [23] that perturbation of RNAP binding energy significantly changes promoter activity, thus affecting gene expression. The binding free energies of RNAP to cro and cI promoters play a key role for the generation of proteins.…”

“…By using lysis frequency as a sensitivity measure, [21] simulated a mutation model introduced by [22] and concluded that spontaneous switching from lysogen to lysis depends sensitively on model parameters. By systematically perturbing binding energies with ±1 kcal/mol, [23] concluded that lysogenic activity at promoter remains stable under this perturbation. In this paper we investigate bifurcation by using bistable range as a system robustness measure.…”

Transcriptional regulation by the numbers: models

“…The conceptual basis of this class of models is the idea that the expression level of the gene of interest can be deduced by examining the equilibrium probabilities that the DNA associated with that gene is occupied by various molecules -these include RNAP and a battery of transcription factors (TFs) such as repressors and activators. There is a long-standing tradition of using these ideas to unravel the dynamics of gene expression systems -particularly important examples being associated with the famed lac operon and phage lambda systems [18,[21][22][23][24][25][26]. Importantly, the thermodynamic models can serve as input to more general chemical kinetic models.…”

Mathematical modeling of the lambda switch: A fuzzy logic approach

“…They also suggested an interesting explanation for the so-called stability puzzle of the switch in terms of bifurcations induced by changes in the CI degradation rate. Bakk et al (2004) studied the sensitivity of the right operator using new experimental data.…”

“…: 2 In a preliminary version of this paper we used the function a r (r,0) provided in (Bakk et al, (2004). However, the model in (Bakk et al, (2004) does not take into account the experimental evidence demonstrating cooperativity between the O R and O L regions.…”