How do control-based approaches enter into biology?

Control is intrinsic to biological organisms, whose cells are in a constant state of sensing and response to numerous external and self-generated stimuli. Diverse means are used to study the complexity through control-based approaches in these cellular systems, including through chemical and genetic manipulations, input-output methodologies, feedback approaches, and feed-forward approaches. We first discuss what happens in control-based approaches when we are not actively examining or manipulating cells. We then present potential methods to determine what the cell is doing during these times and to reverse-engineer the cellular system. Finally, we discuss how we can control the cell's extracellular and intracellular environments, both to probe the response of the cells using defined experimental engineering-based technologies and to anticipate what might be achieved by applying control-based approaches to affect cellular processes. Much work remains to apply simplified control models and develop new technologies to aid researchers in studying and utilizing cellular and molecular processes.