Funneled landscape leads to robustness of cell networks: yeast cell cycle. PLoS Comput. Biol. 2:e147. doi: 10.1371/journal.pcbi.0020147

We uncovered the underlying energy landscape for a cellular network. We discovered that the energy landscape of the yeast cell-cycle network is funneled towards the global minimum (G0/G1 phase) from the experimentally measured or inferred inherent chemical reaction rates. The funneled landscape is quite robust against random perturbations. This naturally explains robustness from a physical point of view. The ratio of slope versus roughness of the landscape becomes a quantitative measure of robustness of the network. The funneled landscape can be seen as a possible realization of the Darwinian principle of natural selection at the cellular network level. It provides an optimal criterion for network connections and design. Our approach is general and can be applied to other cellular networks