Control and Systems Fundamentals

All cells contain DNA, RNA, proteins and other smaller molecules involved in sig-naling and energy transfer and thus function as biochemical factories of a broadly similar type. Major questions in biology are: how do all these components act together to respond to environmental signals and how does the vast variety of cell types develop? Traditional biology approaches usually study the function of a single gene or protein; however, the response of a cell to an environmental cue is highly complex and is the result of the interactions among many components. These concepts are at the basis of the research field known as " systems biology " [1]. The systems approach to biology benefits from the massive amount of data that is being generated by genomics and proteomics high-throughput technologies. This data provides a global view of gene and protein expression patterns of cells after certain environmental signals, thus offering a unique opportunity to characterize cellular responses to disease and stress, as well as to monitor developmental regulatory processes [2]. Acquiring the data is only the start, as the results later need to be managed and interpreted; a fundamental aspect of systems biology is the development of mathematical models that exploit experimental data in order to understand the complex relationships and interactions among the components of cellular systems. An engineering approach to the study of cellular systems appears highly appropriate and promising [3–6]. From a systems theory viewpoint, a cell is a dy-namical system, which can be completely characterized by a set of variables, called state variables; the state variables of a cellular system may be the whole set of gene or protein expression levels. The cell can also be described as an input/output (I/O) system, composed of simpler interconnected components and able to provide a response , or output, to external stimuli or controlled manipulations, called inputs. Inputs to a cellular system can be physical (e.g., temperature changes or a mechanical stress) or chemical (e.g., drugs, hormones, or nutrients), while measurable outputs can be signals to other cells or the activation of transcription factors. Subsystems within a cell can be identified as being involved in different processes, such as cell growth and maintenance, division, and death [7]. The cell is not only a dynamical system, but it is also a controlled environment. The state variables are typically interconnected in a way able to maintain the basic cell functionalities, even in …