Modeling

Overview

1.Gene Expression Dynamics

Analysis of the problem

The symbol declaration is:

Finally, we assigned each process with a reaction rate constant.

How did we build it?

Figure1: The diagram of reactions was designed in the SimBiology toolbox for MATLAB.

What did it show?

• Before running the model, we had to decide on how the hypoxia response element affects gene expression The pCMV promoter (distincted from HRE) expressed approximately 0.15 nM and the [HRE- pCMV] complex expressed 1.86 nM of luciferase in 12 hours. In our simulations, we show that adding hypoxia response element in our promoter design increases the protein expression approximately 20 times more in hypoxic conditions.

• This data was then used to design an experiment that could be performed in the lab to verify the model. You can visit our results page to see the comparison.

2- The gene expression dynamics of TetR – VP16 system by adding oxygen dependent domain (ODD)

• The main goal of this part, being sensitive of TetR – VP16 system to hypoxia. In order to achieve this, ODD added between TetR and VP16 components.In this way, TetR-ODD-VP16 complex can only initiate the transcription of only weak promoter in hypoxic conditions because of the degradation of the complex by proteasome in oxygen presence. By using this system, we created a novel true/ false mechanism which triggers protein synthesis dependent on oxygen by modifying that has already present pTRE-Tet Off system.
• In order to realize how our system will work. We try to calculate how the protein synthesis will effect under different concentration of O2 at the TetR - ODD - VP16 system.
• Using the SimBiology toolbox for Matlab we created a framework of the pTRE-Tet Off System (Figure 2).