Mathematical Modeling of Bistable Toggle Switch

Kinetic Model of Bistable System

Following Gardner's Work...

Tim Gardner from Jim Collins' Lab of Boston Univeristy published one of the first major papers on genetic toggle switch. In his work, he used a kinetic approach to model the stability of a genetic toggle switch. His equations involved two equations expressing the change in the level of two mutually repressive repressors with respect to time.

Figure 1. Equation Used in Gardner's Model

Figure 2. Variables Used in Gardner's Model

Using this model, Gardner produced the two graphs shown below. The first is a graph of nullclines. Nullcline, also called zero-growth isocline, is a line that represents the set of points at which the rate of change is zero. In this example, the two nullclines shown are where rate of change of repressor 1 (U) and repressor 2 (V) are zero. It is clear that at the intersection of these two nullclines are steady-state points of the system because these are points where the change of both repressor levels with respect to time is zero.

The difference between the two figures with nullclines on left and right is that the system on the left is bistable with the system on the right is mono-stable. F

explain nullclines explain bifurcation

Figure 3. Nullclines for Gardner's Model

figure (trajectory)

Figure 4. Gardner's Bifurcation Region Plots

figure (bifurcation)

explain the effect of changing hill coeff on bifurcation region. explain nullcline

reproduce nullcline and trajectory (explain trajectory)

Figure 5. Bifurcation Region and Trajectory

Development of Our Kinetic Model

moving on, we have developed another kinetic model using the results of the thermodynamic model. gardner = effect of hill coeff on bistability of a system (bifurcation region) new model = effect of various parameters on bistability (highlight and number Kd, pr_Str, basal rate.

as mentioned before, key assumption is is (du/dt , dv/dt = proportional to p_bound)

show equation