Team:Bologna/Modeling

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Contents

Mathematical Model


Fig. 1: Genetic flip-flop


Let us pose: F.jpg


The genetic circuit in Figure 1 can be modeled with the following equations:

Equa1.jpg

Where:

Tab.jpg

In the model we distinguish between LacI protein binded to repressor IPTG F001.jpg and protein free F002.jpg.

Since F003.jpg and considering the law of mass action F004.jpg we can write F005.jpg.

Posing:

F006.jpg
F007.jpg

The equations (1.1) and (1.2) can be written in adimensional form:

F008.jpg

Equibrium conditions

If we assume that:

  1. to be under conditions of equilibrium F009.jpg;
  2. all the entries are void F010.jpg;
  3. F011.jpg the affinity of the repressor for the operator site is high, F012.jpg for as we have been defined it will surely be smaller of one so F013.jpg;
  4. the cooperativity is the same both for the LacI and for TetR and it is worth 2;

then the equilibrium equations are:

F013.jpg

The figure 2 has been gotten with both the aces in logarithmic staircase and hypothesizing that ]F014.jpg. There are three point of equilibrium, the blue points to the extreme are stable while the red point to the center is unstable. If we maintain constant a parameter (F015.jpg or F016.jpg) and we make to vary the other is possible to notice that all of a sudden a bifurcation is had, because from three points of equilibrium us neither only one stable.

If it is set F017.jpg it is possible to get figure 3 in which an only point of stable equilibrium is had. This means that is present so much TetR inside the cell and there is little LacI because the gene of LacI is inhibited from the protein TetR that has been synthesized thanks to the entry of IPTG inside the cell.

If instead it is hypothesized that File:F018.jpg it is possible to get the figure 4 in which an only point of stable equilibrium is had. This means that has been produced a lot of LacI that has gone to inhibit the gene that synthesizes TetR after having induced the cell with the UVc. This new point of equilibrium represents the state in which LacI is ON while TetR is OFF.

Bifurcation lines are illustrated in figure 6 for three different values of cooperativity (1.5, 2, 2.5). It is supposed that the cooperativity is always the same one both for LacI and for TetR. The figure 6 is always gotten in logarithmic staircase in function of (F015.jpg and F016.jpg). The bistable region lies inside of each pair of curves.

Knowing that and the law of mass action
F2a.jpg
is possible write
F3.jpg
where we can replace
F4.jpg
represents the entry of IPTG inside the cell. The same thing can be done even for LexA obtaining
F5.jpg
where
F6.jpg
represents the UV radiation.

Placing:

F7.jpg

The dimensionless equations are:

F8.jpg

Equibrium conditions

Hypothesizing: to be under conditions of equilibrium;

all the entries are void (); the affinity of the repressor for the operator site is high, for as we have been defined it will surely be smaller of one so ;

the cooperativity is the same both for the LacI and for TetR and it is worth 2; the equations become:

Bibliography

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