ETHZ/Simulations

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Contents

Basic Model

Constitutively produced proteins

Model01.png

Learning system

Model02.png

Reporter system

Model03.png

System Equations

Constitutively produced proteins

Eq01.png

Learning system

Eq02.png

Reporter system

Eq03.png

Allosteric regulation

Eq04.png


Comments

Note that the three constitutively produced proteins R, S and L exist in two different forms: as free proteins and in complexes they build with IR, IS and IL, respectively. The total amount of protein is denoted with a subscript t (e.g. Rt) in the above formulas. The amount of protein existing as complex is denoted with a superscript * (e.g. R*). The difference is the amount of free protein (e.g. Rt - R*).

In this new formulation of the model equations, the characterization is more amenable to human interpretation (although equivalent to the previous formuation). The promoters are now characterized by their maximum transcription rate (cimax) and the basic production (aX), which gives the 'leakage' if the gene is fully inhibited. Note that in the given mathematical formulation the basic production is specified as a percentage of the max. transcription rate and is therefore unitless.

Model Parameters

Parameter Value Description Comments
c1max max. transcription rate of constitutive promoter
c2max max. transcription rate of luxR-activated promoter
aQ2,R 0.1 - 0.2 basic production of Q2/R-inhibited genes Reference: discussion with Jörg and Sven
aQ2 0.1 - 0.2 basic production of Q2-inhibited genes Reference: discussion with Jörg and Sven
aQ1,S 0.1 - 0.2 basic production of Q1/S-inhibited genes Reference: discussion with Jörg and Sven
aQ1 0.1 - 0.2 basic production of Q1-inhibited genes Reference: discussion with Jörg and Sven
aQ2,S 0.1 - 0.2 basic production of Q2/S-inhibited genes Reference: discussion with Jörg and Sven
aQ1,R 0.1 - 0.2 basic production of Q1/R-inhibited genes Reference: discussion with Jörg and Sven
dR 0.06 degradation of lacI Ref. [4] --please only add parameter values with proper dimensions,
a number like this is useless (Uhrm 04:43, 13 September 2007 (EDT))--
dS 1e-5 [pro sec] degradation of tetR Ref bs2000 Nature 405:590-593
dL degradation of luxR
dQ1 7e-4 [pro sec] degradation of cI Ref arm1998 Genetics 149:1633-1648
dQ2 degradation of p22cII
dYFP degradation of YFP
dGFP degradation of GFP
dRFP degradation of RFP
dCFP degradation of CFP
dIL degradation of AHL-luxR activator
dIR degradation of IPTG-lacI repressor
dIS degradation of aTc-tetR repressor
cQ1,1 promoter strength (R/Q2 inhibited) maybe Ref. [5] can be of help here (for inhibition of R)
cQ1,2 promoter strength (L activated/Q2 inhibited)
cQ2,1 promoter strength (S/Q1 inhibited) maybe Ref. [5] can be of help here (for inhibition of Q1)
cQ2,2 promoter strength (L activated/Q1 inhibited) maybe Ref. [5] can be of help here (for inhibition of Q1)
cYFP promoter strength (S/Q1 inhibited) see also cQ2,1
cGFP promoter strength (R/Q2 inhibited) see also cQ1,1
cRFP promoter strength (S/Q2 inhibited)
cCFP promoter strength (R/Q1 inhibited)
KR 1.3e-3 - 2e-3 [mM/h] lacI repressor dissociation constant lower value is from Ref. [2], higher value is from Ref. [5]
KIR 1.5e-10 [mM/h] IPTG-lacI repressor dissociation constant Ref. [5]
KS tetR repressor dissociation constant
KIS aTc-tetR repressor dissociation constant
KL luxR activator dissociation constant
KIL AHL-luxR activator dissociation constant
KQ1 2e-3 [mM/h] cI repressor dissociation constant Ref. [5]
KQ2 p22cII repressor dissociation constant
nR 1 lacI repressor Hill cooperativity Ref. [5]
nIR 2 IPTG-lacI repressor Hill cooperativity Ref. [5]
nS 3 tetR repressor Hill cooperativity Ref. [3]
nIS aTc-tetR repressor Hill cooperativity
nL 1 luxR activator Hill cooperativity Ref. [3]
nIL 1 AHL-luxR activator Hill cooperativity Ref. [3]
nQ1 1.9 cI repressor Hill cooperativity Ref. [5]
nQ2 p22cII repressor Hill cooperativity

References

  1. A synthetic time-delay circuit in mammalian cells and mice (http://www.pnas.org/cgi/content/abstract/104/8/2643)
  2. Detailed map of a cis-regulatory input function (http://www.pnas.org/cgi/content/full/100/13/7702?ck=nck)
  3. Parameter Estimation for two synthetic gene networks (http://ieeexplore.ieee.org/iel5/9711/30654/01416417.pdf)
  4. Supplementary on-line information for "A Synthetic gene-metabolic oscillator" (no link)
  5. Genetic network driven control of PHBV copolymer composition (http://doi:10.1016/j.jbiotec.2005.08.030)

Variable Mapping

Variable Compound
R lacI
IR IPTG
S tetR
IS aTc
L luxR
IL AHL
Q1 cI
Q2 p22cII