Understanding Complex Regulatory Systems: Integrating Molecular Biology and Systems Analysis

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Abstract
In this article, the application of systems analysis to complex regulatory phenomena in biology was reviewed. It is regarded as an emerging interdisciplinary field of systems biology based on the extensive use of a range of mathematical modeling tools allowing the integration of various regulation levels - from the molecular level to the level of the entire system. Understanding the complex biological systems relies upon the analysis of structure, design, methods of control/coordination and dynamics. The methodology of analysis is presented by considering examples from cellular signaling networks and the immune response regulation. The concepts of feedback and feedforward regulation, modularity and redundancy, which are central for the robust performance of biological systems, are discussed. Some typical structural and regulatory patterns in molecular networks underlying certain types of response behavior (e.g. biphasic response) are described, and the foundations of the computational modeling of complex biological processes grounded in the mathematical systems theory and information-theoretic approaches are outlined. We present a case study on the robustness of the dendritic cell (DC)-based cytotoxic Tlymphocyte (CTL) priming aimed at identifying the control parameters, which relies upon mathematical modeling in conjunction with experimental examination.