Try the new BioModels platform (beta)
BioModels Database logo

BioModels Database

spacer

BIOMD0000000325 - Palini2011_Minimal_2_Feedback_Model

 

 |   |   |  Send feedback
Reference Publication
Publication ID: 21451590
Palani S, Sarkar CA.
Synthetic conversion of a graded receptor signal into a tunable, reversible switch.
Mol. Syst. Biol. 2011 Mar; 7: 480
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, USA.  [more]
Model
Original Model: BIOMD0000000325.origin
Submitter: Santhosh Palani
Submission ID: MODEL1102160000
Submission Date: 16 Feb 2011 22:03:28 UTC
Last Modification Date: 29 Nov 2011 12:07:14 UTC
Creation Date: 31 Mar 2011 04:12:08 UTC
Encoders:  Lukas Endler
   Santhosh Palani
set #1
bqbiol:hasVersion Gene Ontology transmembrane histidine kinase cytokinin receptor activity
Gene Ontology phosphorelay signal transduction system
bqbiol:hasTaxon Taxonomy Saccharomyces cerevisiae
Notes

This is the model of the minmal 2 feedback switch described in the article:
Synthetic conversion of a graded receptor signal into a tunable, reversible switch.
Santhosh Palani and Casim A. Sarkar, 2011, Molecular Systems Biology 7:480; doi: 10.1038/msb.2011.13

The ability to engineer an all-or-none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network switches have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (nH420), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady-state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal-transduction pathways.

This model is parametrised for a transcription factor and receptor feedback strength of 3, TFs = 3 and Rs = 3. To reproduce figure 1 E, the parameters TFs and Rs have to be varied accordingly.

Nomenclature for the model:
L : Ligand
R : Receptor
C : Ligand-Receptor Complex
I : Inactive Transcription Factor
X : C bound to I
A : Active Transcription Factor

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use .
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 21451590 Submission Date: 16 Feb 2011 22:03:28 UTC Last Modification Date: 29 Nov 2011 12:07:14 UTC Creation Date: 31 Mar 2011 04:12:08 UTC
Mathematical expressions
Reactions
R_expression R_degradation R_L_binding C_degradation
C_I_binding I_activation X_degradation A_degradation
I_expression I_degradation    
Physical entities
Compartments Species
cell L R C
I X A
Global parameters
BR Rs KD kdegR
kon koff kdegC k1
k2 k3 kdegX kdegA
BI TFs kdegI  
Reactions (10)
 
 R_expression  → [R];   {A}
 
 R_degradation [R] → ;  
 
 R_L_binding [R] + [L] ↔ [C];  
 
 C_degradation [C] → ;  
 
 C_I_binding [C] + [I] ↔ [X];  
 
 I_activation [X] → [C] + [A];  
 
 X_degradation [X] → ;  
 
 A_degradation [A] → ;  
 
 I_expression  → [I];   {A}
 
 I_degradation [I] → ;  
 
  Spatial dimensions: 3.0  Compartment size: NaN
 
 L
Compartment: cell
Initial concentration: 0.1
 
 R
Compartment: cell
Initial concentration: 1.0
 
 C
Compartment: cell
Initial concentration: 0.0
 
 I
Compartment: cell
Initial concentration: 1.0
 
 X
Compartment: cell
Initial concentration: 0.0
 
 A
Compartment: cell
Initial concentration: 0.0
 
Global Parameters (15)
 
 BR
Value: 0.005
Constant
 
 Rs
Value: 3.0
Constant
 
 KD
Value: 200.0
Constant
 
 kdegR
Value: 0.005
Constant
 
 kon
Value: 0.001
Constant
 
 koff
Value: 0.05
Constant
 
 kdegC
Value: 0.01
Constant
 
 k1
Value: 1.0
Constant
 
 k2
Value: 5.0
Constant
 
 k3
Value: 45.0
Constant
 
 kdegX
Value: 0.005
Constant
 
 kdegA
Value: 0.005
Constant
 
 BI
Value: 0.005
Constant
 
 TFs
Value: 3.0
Constant
 
 kdegI
Value: 0.005
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000325

Curator's comment: (updated: 31 Mar 2011 05:10:01 BST)

Ligand concentration response curve as in figure 1B of the publication. All calculation were performed using Copasi v4.6.33. Two logarithmic parameter scans over the the given ligand range with steady state determination were combined in the graph. For the low activity state, the systems initial conditions were taken from the steady state values at L = 0.001, for the high activity from L = 0.2.

spacer
spacer