Imperial College/Courses/Spring2008/Synthetic Biology/Computer Modelling Practicals/Practical 2: Difference between revisions

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In this section, ...
In this section, we explore a model to represent constitutive gene expression. The model is based on a simple interpretation of the central dogma: gene --> mRNA --> Protein.
To start, launch the CellDesigner Application: Double Click on the Icon found on your Desktop.
Then follow the instructions below to build the model.




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!CellDesigner Instructions
!CellDesigner Instructions
|-
|-
| <center><math>
|  
Gene \xrightarrow{k_{1}} mRNA \xrightarrow{k_{2}} Protein
<center><math> Gene \rightarrow mRNA \rightarrow Protein </math></center>
</math></center>
|  
|  
* '''Define the topology of the reaction network''':
* '''Define the topology of the reaction network''':
** Open a NEW document: File -> New.
** Download this [[Media:Constitutive_Gene_Expression_No_Kinetics.xml| File]], and Open it with CellDesigner.
** Create ....
[[Image:Constitutive_Gene_Expression.png|200px|Constitutive Gene Expression]]
* Save your model
|-
|-
|  
|  
Following the Law of Mass action, the dynamic of the system is described as:  
Following the law of mass action, we can write:  
<center><math>
<center><math>
\begin{alignat}{2}
\begin{alignat}{2}
\frac{d[mRNA]}{dt} = k_{1} - d_{1}*[mRNA] \\
\frac{d[mRNA]}{dt} = k_{1} - d_{1}[mRNA] \\
\frac{d[Protein]}{dt} =  k_{2}*[mRNA] - d_{2}*[Protein] \\
\frac{d[Protein]}{dt} =  k_{2}[mRNA] - d_{2}[Protein] \\
\end{alignat}
\end{alignat}
</math></center>
</math></center>
|  
|  
* Edit Reaction_1, ....
* k_1 is the transcription rate. It is considered constant, and depends on ...
* Save your model.
* d_1 is the mRNA degradation rate of the mRNA. The typical half-life of mRNAs in E.Coli has been measured to be between 2min and 8min (average 5min).
* k_2 is the translation rate. It is considered constant, and depends on ...
* d_2 is the protein degradation rate. Here, we will only consider very stable proteins, not engaged in any active degradation pathways. In that case, we can approximate the degradation of the protein to be only due to the dilution effect happening during cell division. Cell division will be 30min.
|}
 
'''Questions:'''
* From the ODE system given, write down the steady-state expression of [mRNA] and [Protein], with regards to k_1, k_2, d_1, d_2.
* Knowing that average mRNA per gene is 2.5 in E.Coli, what is the average transcription rate ?
* Knowing that the average Protein per gene is 1000 in E.Coli, what is the average translation rate ?
* Define all the necessary kinetics laws on the model, and create all the appropriate parameters.
* Run a simulation, and comment on the simulation ouputs.
 
{| border="1"  cellpadding="10" cellspacing="2" style="width:700px; border:3px green"
!Model
!CellDesigner Instructions
|-
|-
| Simulate the dynamical behaviour
|  
<center><math> Gene \rightarrow  Protein </math></center>
|
* ...
[[Image:Constitutive_Gene_Expression.png|200px|Constitutive Gene Expression]]
|-
|
Following the law of mass action, we can write:
<center><math>
\begin{alignat}{2}
\frac{d[Protein]}{dt} =  synthesisRate - degrationRate[Protein] \\
\end{alignat}
</math></center>
|  
|  
* ...
* ...
* Press Execute, and check results.
|}
|}


* '''Questions:'''
* ...
** ...
 


* '''Additional Resources:'''
* '''Additional Resources:'''
** ...
** [http://redpoll.pharmacy.ualberta.ca/CCDB/cgi-bin/STAT_NEW.cgi E.Coli Statistics]


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</font><br>
</font><br>
</div>
</div>
In this section, ....
{| border="1"  cellpadding="10" cellspacing="2" style="width:700px; border:3px green"
!Model
!CellDesigner Instructions
|-
|
<center><math> Gene \rightarrow mRNA \rightarrow Protein </math></center>
|
* '''Define the topology of the reaction network''':
**
|-
|
Following the law of mass action, we can write:
|
* ...
|}
'''Questions:'''
* ...


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</font><br>
</font><br>
</div>
</div>
In this section, ....
{| border="1"  cellpadding="10" cellspacing="2" style="width:700px; border:3px green"
!Model
!CellDesigner Instructions
|-
|
<center><math> Gene \rightarrow mRNA \rightarrow Protein </math></center>
|
* '''Define the topology of the reaction network''':
**
|-
|
Following the law of mass action, we can write:
|
* ...
|}
'''Questions:'''
* ...

Revision as of 12:04, 13 January 2008

Synthetic Biology (Spring2008): Computer Modelling Practicals

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Practical 2


Objectives:

  • To explore computationally some simple genetic motifs:
    • Constitutive gene expression.
    • Activated and Repressed gene expression.
    • Positive and Negative feedback gene expression.

Deliverables

  • A report is expected by ... (Word or PDF format, sent to XXX@XXX)
  • When you find in the text (illustration needed), it means that you will have to provide an image export of your simulation results in your report.


Part I: Constitutive Gene Expression


In this section, we explore a model to represent constitutive gene expression. The model is based on a simple interpretation of the central dogma: gene --> mRNA --> Protein.


Model CellDesigner Instructions
[math]\displaystyle{ Gene \rightarrow mRNA \rightarrow Protein }[/math]
  • Define the topology of the reaction network:
    • Download this File, and Open it with CellDesigner.

Constitutive Gene Expression

Following the law of mass action, we can write:

[math]\displaystyle{ \begin{alignat}{2} \frac{d[mRNA]}{dt} = k_{1} - d_{1}[mRNA] \\ \frac{d[Protein]}{dt} = k_{2}[mRNA] - d_{2}[Protein] \\ \end{alignat} }[/math]
  • k_1 is the transcription rate. It is considered constant, and depends on ...
  • d_1 is the mRNA degradation rate of the mRNA. The typical half-life of mRNAs in E.Coli has been measured to be between 2min and 8min (average 5min).
  • k_2 is the translation rate. It is considered constant, and depends on ...
  • d_2 is the protein degradation rate. Here, we will only consider very stable proteins, not engaged in any active degradation pathways. In that case, we can approximate the degradation of the protein to be only due to the dilution effect happening during cell division. Cell division will be 30min.

Questions:

  • From the ODE system given, write down the steady-state expression of [mRNA] and [Protein], with regards to k_1, k_2, d_1, d_2.
  • Knowing that average mRNA per gene is 2.5 in E.Coli, what is the average transcription rate ?
  • Knowing that the average Protein per gene is 1000 in E.Coli, what is the average translation rate ?
  • Define all the necessary kinetics laws on the model, and create all the appropriate parameters.
  • Run a simulation, and comment on the simulation ouputs.
Model CellDesigner Instructions
[math]\displaystyle{ Gene \rightarrow Protein }[/math]
  • ...

Constitutive Gene Expression

Following the law of mass action, we can write:

[math]\displaystyle{ \begin{alignat}{2} \frac{d[Protein]}{dt} = synthesisRate - degrationRate[Protein] \\ \end{alignat} }[/math]
  • ...
  • ...


Part II: Activated and Repressed Gene Expression

In this section, ....


Model CellDesigner Instructions
[math]\displaystyle{ Gene \rightarrow mRNA \rightarrow Protein }[/math]
  • Define the topology of the reaction network:

Following the law of mass action, we can write:

  • ...

Questions:

  • ...

Part III: Positive and Negative Feedback

In this section, ....


Model CellDesigner Instructions
[math]\displaystyle{ Gene \rightarrow mRNA \rightarrow Protein }[/math]
  • Define the topology of the reaction network:

Following the law of mass action, we can write:

  • ...

Questions:

  • ...
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