Team:KULeuven/Model/Output

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Output

Position in the system

The output system is one of three modules directly linked to the input. The output system is a simple gene regulation, of which transcription is activated by tetR. The output signal is GFP (green fluorescent protein).

In the applied project of dealing with Crohn's disease this would be replaced by the drug necessary to cure the local inflammation. The drug concentration would be proportional to the amount of local inflammation sensed.

Describing the system

ODE's

Parameters

*Parameter values (Output)*
Name	Value	Comments	Reference
Degradation Rates
d_GFP	d_LVA = 2.814E-4 s^-1	LVA-tag reduces lifetime to 40 minutes	[1] [4]
d_{mRNA_GFP}	0.0023 s^-1		[2]
Transcription Rates
TetR_var_transcr_rate	p(TetR) dependent	(GFP) between 5E-5 and 0.0125 s^-1 ~ [aTc]	[3]
Translation Rates
k_GFP	0.167 s^-1	translation rate for B0032 RBS (0.3 relative efficiency)	[5]

Models

CellDesigner (SBML file)

Matlab (SBML file)

Simulations

Several simulations were conducted, the following two show the transient respons and eventual saturation of the output system to a low and a high step signal as input, respectively. We see that there is a great distinction in the number of CFP molecules between the two input signals.

Next figure shows the switching behaviour of the output system to an light signal turning off and on:

Sensitivity Analysis

References

Bibliography

[1]	“ETHZ/Parameters - IGEM07”; http://parts.mit.edu/igem07/index.php/ETHZ/Parameters.

[2]	J.A. Bernstein et al., “Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, Jul. 2002, pp. 9697–9702.

[3]	M. Bon, S.J. McGowan, and P.R. Cook, “Many expressed genes in bacteria and yeast are transcribed only once per cell cycle,” FASEB J., vol. 20, Aug. 2006, pp. 1721-1723.

[4]	J.B. Andersen et al., “New Unstable Variants of Green Fluorescent Protein for Studies of Transient Gene Expression in Bacteria,” Applied and Environmental Microbiology, vol. 64, Jun. 1998, pp. 2240–2246.

[5]	“Part:BBa B0032 - partsregistry.org”; http://partsregistry.org/Part:BBa_B0032.

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 | d<sub>LVA</sub> = 2.814E-4 s<sup>-1</sup>
 | LVA-tag reduces lifetime to 40 minutes
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 | d<sub>mRNA_GFP</sub>
 | 0.0023 s<sup>-1</sup>
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 ! colspan="4" style="border-bottom: 1px solid #003E81;" | Transcription Rates
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 | p(TetR) dependent
 | (GFP) between 5E-5 and 0.0125 s<sup>-1</sup> ~ [aTc]
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 ! colspan="4" style="border-bottom: 1px solid #003E81;" | Translation Rates
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 | 0.167 s<sup>-1</sup>
 | translation rate for B0032 RBS (0.3 relative efficiency)
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 |}