TY - JOUR
T1 - Analysis and extension of a biochemical network model using robust control theory
AU - Kim, Jongrae
AU - Valeyev, Najil
AU - Postlethwaite, Ian
AU - Heslop-Harrison, Pat
AU - Cho, Kwang-Hyun
AU - Bates, Declan
N1 - robustness analysis, structured singular value, Dictyostelium, systems biology
PY - 2009
Y1 - 2009
N2 - Mathematical models of biological processes which have been observed in vivo to be highly robust to intracellular and environmental variations should themselves display appropriate levels of robustness when analysed in silico. This paper uses techniques from robust control theory to analyse and extend a mathematical model of the interacting proteins underlying adenosine 3′, 5′-cyclic monophosphate (cAMP) oscillations in aggregating Dictyostelium cells. Starting with a previously proposed ‘minimal’ model, we show how robustness analysis using the structured singular value can identify points of structural fragility in the network. By combining these results with insights from recent results from the experimental literature, we show how the original model can be augmented with some important additional modules, comprising networks involving IP3 and Ca2+. By analysing the robustness of our new extended model, we are able to show that dynamic interactions between the different modules play a pivotal role in generating robust cAMP oscillations; thus, significantly improving our understanding of the design principles underlying this complex biological syste
AB - Mathematical models of biological processes which have been observed in vivo to be highly robust to intracellular and environmental variations should themselves display appropriate levels of robustness when analysed in silico. This paper uses techniques from robust control theory to analyse and extend a mathematical model of the interacting proteins underlying adenosine 3′, 5′-cyclic monophosphate (cAMP) oscillations in aggregating Dictyostelium cells. Starting with a previously proposed ‘minimal’ model, we show how robustness analysis using the structured singular value can identify points of structural fragility in the network. By combining these results with insights from recent results from the experimental literature, we show how the original model can be augmented with some important additional modules, comprising networks involving IP3 and Ca2+. By analysing the robustness of our new extended model, we are able to show that dynamic interactions between the different modules play a pivotal role in generating robust cAMP oscillations; thus, significantly improving our understanding of the design principles underlying this complex biological syste
U2 - 10.1002/rnc.1528
DO - 10.1002/rnc.1528
M3 - Article
VL - 20
SP - 1017
EP - 1026
JO - International Journal of Robust and Nonlinear Control
JF - International Journal of Robust and Nonlinear Control
SN - 1049-8923
IS - 9
ER -