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__NOTOC__
__NOTOC__
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= Parameters for the EducatETH <i>E. coli</i> system =
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= Parameters for the educatETH <i>E.coli</i> system =
<p>
<p>
-
In order to provide as realistic simulation results as possible, and to find good estimates for the simulation parameters, we performed an intensive literature review. However, not all parameters could be found in the literature. Furthermore, one has to take into account that biological parameters cannot be estimated to a very high precision.
+
In order to ensure that our simulation results match the biology as close as possible, we tried to find good estimates for the biological system parameters. To this end, we performed an extensive literature review. However, not all parameters were found in the literature, especially those which do not refer to vastly used proteins. Whenever this was the case, logical estimates were provided by our biologists based on empirical values.
</p><br>
</p><br>
== Model Parameters ==
== Model Parameters ==
-
{| class="wikitable" border="1" cellspacing="0" cellpadding="2" style="text-align:left; margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;"
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! Parameter                         
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=== General parameters ===
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! Value
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{| class="wikitable" width="100%" border="1" cellspacing="0" cellpadding="2" style="text-align:left; margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;"
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! Description
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!width="10%"| Parameter                         
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! Comments
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!width="10%"| Value
-
!
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!width="20%"| Description
-
! Parameter                       
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!width="60%"| Comments
-
! Value
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-
! Description
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-
! Comments
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|-
|-
| c<sub>1</sub><sup>max</sup>
| c<sub>1</sub><sup>max</sup>
Line 27: Line 104:
| max. transcription rate of constitutive promoter (per gene)
| max. transcription rate of constitutive promoter (per gene)
| promoter no. J23105; Estimate
| promoter no. J23105; Estimate
-
|
+
|-
| c<sub>2</sub><sup>max</sup>
| c<sub>2</sub><sup>max</sup>
| 0.01 [mM/h]
| 0.01 [mM/h]
Line 37: Line 114:
| high-copy plasmid number
| high-copy plasmid number
| Estimate
| Estimate
-
|
+
|-
| l<sup>lo</sup>
| l<sup>lo</sup>
| 5
| 5
Line 47: Line 124:
| basic production levels
| basic production levels
| Estimate
| Estimate
-
|
 
-
|
 
-
|
 
-
|
 
-
|
 
|-
|-
-
| Degradation constants  
+
|}
-
|
+
 
-
|  
+
=== Degradation constants ===
-
|  
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{| class="wikitable" width="100%" border="1" cellspacing="0" cellpadding="2" style="text-align:left; margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;"
-
|  
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!width="10%"| Parameter                       
-
|
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!width="10%"| Value
-
|
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!width="20%"| Description
-
|
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!width="60%"| Comments
|-
|-
| d<sub>LacI</sub>
| d<sub>LacI</sub>
Line 66: Line 138:
| degradation of LacI
| degradation of LacI
| Ref. [10]
| Ref. [10]
-
|
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|-
| d<sub>TetR</sub>
| d<sub>TetR</sub>
|  
|  
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| degradation of LuxR
| degradation of LuxR
| Ref: [6]
| Ref: [6]
-
|
 
-
|
 
-
|
 
-
|
 
-
|
 
|-
|-
| d<sub>CI</sub>
| d<sub>CI</sub>
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| degradation of CI
| degradation of CI
| Ref. [7]
| Ref. [7]
-
|
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|-
| d<sub>P22CII</sub>
| d<sub>P22CII</sub>
|  
|  
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| degradation of YFP
| degradation of YFP
| suppl. mat. to Ref. [8] corresponding to a half life of 110min
| suppl. mat. to Ref. [8] corresponding to a half life of 110min
-
|
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|-
| d<sub>GFP</sub>
| d<sub>GFP</sub>
| 6.3e-3 [1/min]
| 6.3e-3 [1/min]
Line 110: Line 177:
| degradation of RFP
| degradation of RFP
| in analogy to YFP
| in analogy to YFP
-
|
+
|-
| d<sub>CFP</sub>
| d<sub>CFP</sub>
| 6.3e-3 [1/min]
| 6.3e-3 [1/min]
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| in analogy to YFP
| in analogy to YFP
|-
|-
-
| Dissociation constants
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|}
-
|  
+
 
-
|  
+
=== Dissociation constants ===
-
|  
+
 
-
|
+
{| class="wikitable" width="100%" border="1" cellspacing="0" cellpadding="2" style="text-align:left; margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;"
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|  
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!width="10%"| Parameter                       
-
|  
+
!width="10%"| Value
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!width="20%"| Description
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!width="60%"| Comments
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|-
 +
| K<sub>LacI</sub>
|  
|  
 +
* 0.1 - 1 [pM]
 +
* 800 [nM]
 +
| LacI repressor dissociation constant
|  
|  
 +
* Ref. [2]
 +
* Ref. [12]
|-
|-
-
| K<sub>LacI</sub>
 
-
| 0.1 - 1 [pM]
 
-
| LacI repressor dissociation constant
 
-
| Ref. [2]
 
-
|
 
| K<sub>IPTG</sub>
| K<sub>IPTG</sub>
| 1.3 [&#181;M]
| 1.3 [&#181;M]
Line 140: Line 211:
| TetR repressor dissociation constant
| TetR repressor dissociation constant
| Ref. [1]
| Ref. [1]
-
|
+
|-
| K<sub>ATC</sub>
| K<sub>ATC</sub>
| 893 [pM]
| 893 [pM]
Line 150: Line 221:
| LuxR activator dissociation constant
| LuxR activator dissociation constant
| Ref: [6]
| Ref: [6]
-
|
+
|-
| K<sub>AHL</sub>
| K<sub>AHL</sub>
| 0.09 - 1 [&#181;M]
| 0.09 - 1 [&#181;M]
Line 164: Line 235:
*Ref. [12]
*Ref. [12]
*starting with values of Ref. [6] and using Ref. [3]
*starting with values of Ref. [6] and using Ref. [3]
-
|
+
|-
| K<sub>P22CII</sub>
| K<sub>P22CII</sub>
| 0.577 [&#181;M]
| 0.577 [&#181;M]
| P22CII repressor dissociation constant
| P22CII repressor dissociation constant
-
| Ref. [11]. Note that they use a protein CII and we have P22CII. Does that match?
+
| Ref. [11]
|-
|-
-
|Hill cooperativity
+
|}
-
|
+
 
-
|
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=== Hill cooperativity ===
-
|
+
{| class="wikitable" width="100%" border="1" cellspacing="0" cellpadding="2" style="text-align:left; margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;"
-
|
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!width="10%"| Parameter                       
-
|
+
!width="10%"| Value
-
|
+
!width="20%"| Description
-
|
+
!width="60%"| Comments
-
|
+
|-
|-
| n<sub>LacI</sub>
| n<sub>LacI</sub>
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* Ref. [5]
* Ref. [5]
* Ref. [12]
* Ref. [12]
-
|
+
|-
| n<sub>IPTG</sub>
| n<sub>IPTG</sub>
| 2
| 2
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| TetR repressor Hill cooperativity
| TetR repressor Hill cooperativity
| Ref. [3]
| Ref. [3]
-
|
+
|-
| n<sub>ATC</sub>
| n<sub>ATC</sub>
| 2 (1.5-2.5)
| 2 (1.5-2.5)
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| LuxR activator Hill cooperativity
| LuxR activator Hill cooperativity
| Ref: [6]
| Ref: [6]
-
|
+
|-
| n<sub>AHL</sub>
| n<sub>AHL</sub>
| 1
| 1
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| CI repressor Hill cooperativity
| CI repressor Hill cooperativity
| Ref. [12]
| Ref. [12]
-
|
+
|-
| n<sub>P22CII</sub>
| n<sub>P22CII</sub>
| 4
| 4
| P22CII repressor Hill cooperativity
| P22CII repressor Hill cooperativity
-
| Ref. [11]. Note that they use a protein CII and we have P22CII. Does that match?
+
| Ref. [11]
|-
|-
|}
|}

Latest revision as of 14:27, 26 October 2007

ETHZ banner.png

 


Parameters for the educatETH E.coli system

In order to ensure that our simulation results match the biology as close as possible, we tried to find good estimates for the biological system parameters. To this end, we performed an extensive literature review. However, not all parameters were found in the literature, especially those which do not refer to vastly used proteins. Whenever this was the case, logical estimates were provided by our biologists based on empirical values.


Model Parameters

General parameters

Parameter Value Description Comments
c1max 0.01 [mM/h] max. transcription rate of constitutive promoter (per gene) promoter no. J23105; Estimate
c2max 0.01 [mM/h] max. transcription rate of LuxR-activated promoter (per gene) Estimate
lhi 25 high-copy plasmid number Estimate
llo 5 low-copy plasmid number Estimate
a 1% basic production levels Estimate

Degradation constants

Parameter Value Description Comments
dLacI 2.31e-3 [1/s] degradation of LacI Ref. [10]
dTetR
  • 1e-5 [1/s]
  • 2.31e-3 [1/s]
degradation of TetR
  • Ref. [9]
  • Ref. [10]
dLuxR 1e-3 - 1e-4 [1/s] degradation of LuxR Ref: [6]
dCI 7e-4 [1/s] degradation of CI Ref. [7]
dP22CII degradation of P22CII
dYFP 6.3e-3 [1/min] degradation of YFP suppl. mat. to Ref. [8] corresponding to a half life of 110min
dGFP 6.3e-3 [1/min] degradation of GFP in analogy to YFP
dRFP 6.3e-3 [1/min] degradation of RFP in analogy to YFP
dCFP 6.3e-3 [1/min] degradation of CFP in analogy to YFP

Dissociation constants

Parameter Value Description Comments
KLacI
  • 0.1 - 1 [pM]
  • 800 [nM]
LacI repressor dissociation constant
  • Ref. [2]
  • Ref. [12]
KIPTG 1.3 [µM] IPTG-LacI repressor dissociation constant Ref. [2]
KTetR 179 [pM] TetR repressor dissociation constant Ref. [1]
KATC 893 [pM] ATC-TetR repressor dissociation constant Ref. [1]
KLuxR 55 - 520 [nM] LuxR activator dissociation constant Ref: [6]
KAHL 0.09 - 1 [µM] AHL-LuxR activator dissociation constant Ref: [6]
KCI
  • 8 [pM]
  • 50 [nM]
CI repressor dissociation constant
  • Ref. [12]
  • starting with values of Ref. [6] and using Ref. [3]
KP22CII 0.577 [µM] P22CII repressor dissociation constant Ref. [11]

Hill cooperativity

Parameter Value Description Comments
nLacI
  • 1
  • 2
LacI repressor Hill cooperativity
  • Ref. [5]
  • Ref. [12]
nIPTG 2 IPTG-LacI repressor Hill cooperativity Ref. [5]
nTetR 3 TetR repressor Hill cooperativity Ref. [3]
nATC 2 (1.5-2.5) ATC-TetR repressor Hill cooperativity Ref. [3]
nLuxR 2 LuxR activator Hill cooperativity Ref: [6]
nAHL 1 AHL-LuxR activator Hill cooperativity Ref. [3]
nCI 2 CI repressor Hill cooperativity Ref. [12]
nP22CII 4 P22CII repressor Hill cooperativity Ref. [11]


References

[http://www.pnas.org/cgi/content/abstract/104/8/2643 [1] Weber W et al.] "A synthetic time-delay circuit in mammalian cells and mice", P Natl Acad Sci USA 104(8):2643-2648, 2007
[http://www.pnas.org/cgi/content/full/100/13/7702?ck=nck [2] Setty Y et al.] "Detailed map of a cis-regulatory input function", P Natl Acad Sci USA 100(13):7702-7707, 2003
[http://ieeexplore.ieee.org/iel5/9711/30654/01416417.pdf [3] Braun D et al.] "Parameter Estimation for Two Synthetic Gene Networks: A Case Study", ICASSP 5:769-772, 2005
[http://www.nature.com/nature/journal/v435/n7038/suppinfo/nature03508.html [4] Fung E et al.] "A synthetic gene--metabolic oscillator", Nature 435:118-122, 2005 (supplementary material)
[http://dx.doi.org/10.1016/j.jbiotec.2005.08.030 [5] Iadevaia S and Mantzais NV] "Genetic network driven control of PHBV copolymer composition", J Biotechnol 122(1):99-121, 2006
[http://dx.doi.org/10.1016/j.biosystems.2005.04.006 [6] Goryachev AB et al.] "Systems analysis of a quorum sensing network: Design constraints imposed by the functional requirements, network topology and kinetic constants", Biosystems 83(2-3):178-187, 2004
[http://www.genetics.org/cgi/content/abstract/149/4/1633 [7] Arkin A et al.] "Stochastic kinetic analysis of developmental pathway bifurcation in phage λ-Infected Escherichia coli cells", Genetics 149: 1633-1648, 1998
[http://download.cell.com/supplementarydata/cell/107/6/739/DC1/index.htm [8] Colman-Lerner A et al.] "Yeast Cbk1 and Mob2 Activate Daughter-Specific Genetic Programs to Induce Asymmetric Cell Fates", Cell 107(6): 739-750, 2001 (supplementary material)
[http://www.nature.com/nature/journal/v405/n6786/abs/405590a0.html [9] Becskei A and Serrano L] "Engineering stability in gene networks by autoregulation", Nature 405: 590-593, 2000
[http://www.biophysj.org/cgi/content/full/89/6/3873?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&volume=89&firstpage=3873&resourcetype=HWCIT [10] Tuttle et al.] "Model-Driven Designs of an Oscillating Gene Network", Biophys J 89(6):3873-3883, 2005
[http://www.pnas.org/cgi/reprint/99/2/679 [11] McMillen LM et al.] "Synchronizing genetic relaxation oscillators by intercell signaling", P Natl Acad Sci USA 99(2):679-684, 2002
[http://www.nature.com/nature/journal/v434/n7037/full/nature03461.html [12] Basu S et al.] "A synthetic multicellular system for programmed pattern formation", Nature 434:1130-1134, 2005

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