Endy:Chassis engineering/VM2.0
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VM2.0 regulation design considerations
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- Stability
- Noise
- analytical stability analysis on very simple model or Routh-Hurwitz analysis for full model
- parameter sensitivity analysis
- Response time
- Better to have this fast or slow (slow response time averages out short time scale fluctuations)
- Noise
- Self-booting/controlled
- Ability to turn on or off
- Portability
- Tunable
- Pros and cons of DNA copy number, promoter strength, repressor affinities etc.
- Efficient
- Minimizing levels of repressor needed
- Minimizing consumption of small molecules
What are the metrics for each of the design considerations?
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Reduced Model
- Two species, RNAP (activator) and repressor
- Continuous differential equations
- MATLAB
- Dimensionless variables, lumped parameters.
- Parameterized for T7 RNAP, "typical" repressor
[math]\displaystyle{
\dot{[u]} = \frac{a_{0}+a_{1}[u]}{1+[u]+[v]^{n}}-[u]\qquad(1)
}[/math]
[math]\displaystyle{
\dot{[v]} = \frac{a_{0}+a_{1}[u]}{1+[u]+[v]^{n}}-[v]\qquad(2)
}[/math]
[math]\displaystyle{ [u] }[/math] = dimensionless concentration of T7 RNAP
[math]\displaystyle{ [v] }[/math] = dimensionless concentration of repressor
Reduced model results
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Species
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- T7 RNAP
- Repressor
- Ribosomes
- Repressible T7 promoter
- T7RNAP-promoter complex
- Repressor-promoter complex
- T7 RNAP mRNA
- Repressor mRNA
- Elongating T7 RNAP
- Elongating Ribosomes
- etc.
Model analysis notes
- A cooperative autogene network can exhibit bistability or monostability depending on parameter values (7.81). Does this apply if there is no cooperativity?
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