Tutorial on modelling signalling pathways
Quick overview of the supporting files
1) Introduction to models that are used in this tutorial:
tutorial introduction (PDF)
2) Course Tutorial Handouts:
Exercise: model building & simulation (PDF)
3) Bistability (MAPK double phosphorylation):
i. Ortega F, Garcés JL, Mas F, Kholodenko BN, Cascante M. Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements. FEBS J 2006 Sep;273(17):3915-26.
[BIOMD0000000258]
Reference : Ortega2006.pdf
SBML file : BIOMD0000000258.xml (to be imported to COPASI for simulation)
COPASI file : ortega_parameterscan_sss.cps (open in COPASI and run parameter scan simulation to get the plot)
ortega_parameterscan_bistable.cps (open in COPASI and run parameter scan simulation to get the plot)
4) MAPK cascade:
i. Huang CY, Ferrell JE Jr. Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10078-83.
[BIOMD0000000009]
Reference : Huang1996.pdf
SBML file : BIOMD0000000009.xml (to be imported to COPASI for simulation)
COPASI file : huang_timecourse.cps (open in COPASI and run Time-course simulation to get the plot)
huang_parameterscan.cps (open in COPASI and run paramter scan to get the plot)
ii. Kholodenko BN. Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. Eur J Biochem. 2000 Mar;267(6):1583-8. -
[BIOMD0000000010]
Reference : Kholodenko2000.pdf
Simulation without negative feedback:
COPASI files : kholodenko.cps (COPASI base file: without negative feedback)
kholodenko_timecourse.cps (open in COPASI and run Time-course simulation to get the plot)
Simulation with Negative feedback:
SBML file : BIOMD0000000010.xml
COPASI file : kholodenko_nf.cps (COPASI file with negative feedback)
kholodenko_nf_timecourse.cps (open in COPASI and run Time-course simulation to get the plots (timecourse and phaseplot)
kholodenko_nf_parameterscan.cps (open in COPASI and run parameter scan to get the plots (timecourse and phaseplot)
5) p53/MDM2 circuit:
Proctor CJ, Gray DA. Explaining oscillations and variability in the p53-Mdm2 system. BMC Syst Biol. 2008 Aug 18;2:75.
Reference : Proctor2008.pdf
i. p53 stabilization by ARF - BIOMD0000000189
SBML file : BIOMD0000000189.xml (to be imported to COPASI for simulation)
COPASI file : proctorARF_timecourse.cps (open in COPASI and run Time-course simulation to get the plot)
ii. p53 stabilization by ATM - BIOMD0000000188
SBML file : BIOMD0000000188.xml (to be imported to COPASI for simulation)
COPASI file : proctorATM_timecourse.cps (open in COPASI and run Time-course simulation to get the plot)
6) Repressilator:
Elowitz MB, Leibler S. A synthetic oscillatory network of transcriptional regulators.
Nature 2000 Jan;403(6767):335-8. -(BIOMD0000000012)
Reference : Elowitz2000.pdf
SBML file : BIOMD0000000012.xml (to be imported to COPASI for simulation)
COPASI file : elowitz_timecourse.cps (open in COPASI and run Time-course simulation to get the plot)
Training materials for model curation