Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.
We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.
Casey
F P
FP
F.P. Casey was with the Center for Applied Mathematics, Cornell University, Ithaca, NY 14853, USA. ferg@cam.cornell.edu
Baird
D
D
Feng
Q
Q
Gutenkunst
R N
RN
Waterfall
J J
JJ
Myers
C R
CR
Brown
K S
KS
Cerione
R A
RA
Sethna
J P
JP
D018797:Cell Cycle Proteins / Q000378:metabolism*; D003198:Computer Simulation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008954:Models, Biological; D012106:Research; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D066246:ErbB Receptors