Team:Michigan/Project/Modeling

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(Sequestillator Modeling)
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= '''<font color=dodgerblue size=6>Sequestillator Modeling</font>''' =
= '''<font color=dodgerblue size=6>Sequestillator Modeling</font>''' =
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The Sequestilator modeling fits in with the Michigan team's pursuit of a greater understanding of the molecular dynamics that promote oscillatory behavior.  In this page, you will find our approaches not only to modeling the Sequestilator, but to similar clocks.
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The creation of a synthetic genetic clock has been considered by many people to be a "holy grail" of synthetic biology.  Elowitz's "Repressilator" was one of the first synthetic clocks constructed, and it paved the way for consideration of other topologies that may promote oscillatory behavior, such as the Atkinson clock.
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A common characteristic of genetic clocks in general is the presence of a negative feedback loop (i.e. A activates B, and B represses A, so by repressing A, B indirectly its own concentration).  In the Repressilator and the Atkinson clock, this repression occurred on the pre-transcriptional level; that is, the repressor protein prevented transcription of the activator gene.
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Repression Feedback Loops:
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Below, we present three topologies of clocks with their modes of repression.
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Let us consider three different clock topologies:
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<div align='center'>[[Image:Picture8.png]]              [[Image:Picture3.png]]                [[Image:Picture2.png]]</div>
<div align='center'>[[Image:Picture8.png]]              [[Image:Picture3.png]]                [[Image:Picture2.png]]</div>
<div align='center'>Post-translational repression        Pre-translational repression                  Pre-transcriptional repression </div>             
<div align='center'>Post-translational repression        Pre-translational repression                  Pre-transcriptional repression </div>             
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Let's add a positive feedback loop to all of them:
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Note that the pre-transcriptional repression topology is the Atkinson clock without the positive feedback loop, and the post-translational clock is the Sequestillator.
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One of the goals of the modeling team is to understand the dynamics of this repression loop - i.e., how does the type of repression effect the robustness of the oscillator and the behavior (amplitude, periodicity, etc.).
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We can answer the first question (robustness) using numerical techniques.
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*Stochastic comparison of all three oscillators
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Revision as of 17:37, 29 October 2008


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Sequestillator Modeling

The creation of a synthetic genetic clock has been considered by many people to be a "holy grail" of synthetic biology. Elowitz's "Repressilator" was one of the first synthetic clocks constructed, and it paved the way for consideration of other topologies that may promote oscillatory behavior, such as the Atkinson clock. A common characteristic of genetic clocks in general is the presence of a negative feedback loop (i.e. A activates B, and B represses A, so by repressing A, B indirectly its own concentration). In the Repressilator and the Atkinson clock, this repression occurred on the pre-transcriptional level; that is, the repressor protein prevented transcription of the activator gene. Below, we present three topologies of clocks with their modes of repression.

Picture8.png Picture3.png Picture2.png
Post-translational repression Pre-translational repression Pre-transcriptional repression

Note that the pre-transcriptional repression topology is the Atkinson clock without the positive feedback loop, and the post-translational clock is the Sequestillator. One of the goals of the modeling team is to understand the dynamics of this repression loop - i.e., how does the type of repression effect the robustness of the oscillator and the behavior (amplitude, periodicity, etc.).

We can answer the first question (robustness) using numerical techniques.


  • Stochastic comparison of all three oscillators