Module-based analysis of the robustness generated by complex feedback regulations in biological networks

Bacterial cells evolve complex networks to survive nutrient starvation. The E. coli ammonia assimilation system consists of many positive and negative feedbacks for synthesizing glutamine and glutamate, the source of most nitrogen-containing compounds. Our objectives are to understand the molecular architecture of how those feedback loops act in concert for enhanced robustness with respect to ammonia depletion. The ammonia assimilation system is decomposed into the hierarchical modular structure in analogy to engineering control architecture. This modular architecture is elaborately designed to solve contradictory design issues. Comparison of biological modules with engineering systems identifies interesting biologically specific design features.