Modeling Celldeath
1. Describing the celldeath system
The cell death mechanism we use should be induced when stimulus 1 (L-arabinose) or stimulus 2 (lactose) and at the same time a cold temperature is applied.
Procedure: We grow the bacteria at the optimal temperature of 37 degrees. Then we produce the protein we wish by applying the correct stimulus. E.g., L-arabinose to produce AFP. After synthesizing the desired amount of protein, we lower the temperature to induce the cell death mechanism.
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PARAMETER TABLE
2. CellDeath Model
3. Simulations
We made a simulation in such a way that the ribokey-RNA is present at a constant value (figure 1). With this assumption, the only variable in the production for CeaB would be CeaB mRNA which linearly increases. Initially the production of CeaB is increasing non-linearly, but after a certain amount of time CeaB production becomes linear (figure 2); at that moment the degradation of CeaB is becoming important as well.
Here, the input of lactose or arabinose is assumed to be constant . To improve this model, it could be updated with a varying input for lactose or arabinose. Also a temperature-varying parameter will be necessary, because the promoter we use is temperature sensitive.
4. Sensitivity analysis
In these graphs, the 'parameters'-axis shows the parameters that are varied in the sensitivity analysis, while the ones along the states axis are the ones monitored as output. The z-axis is a measure for the sensitivity of the parameter under study.
The sensitivity plots are starting from 10 seconds and ending with 10 000 seconds. The importance of sensitivity shifts from the transcription parameter to the degradation parameters .
In nature the transcription parameters maybe will be important for a longer time, but with our simplified model the sensitivity of degradation parameters is already more important than transcription parameters after 1000s.
For optimizing the system in future, we suggest to rebuild the promoter sequence to become higher value for transcription parameters. Another possibility is to lower the degradation parameters by increasing stability of the CeaB protein. The second option will be perhaps more difficult. The parameter scan figures display the results of a possible variation in these parameters.
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