A distinctive feature of many biological systems is their ability to adapt to persistent stimuli or disturbances that would otherwise drive them away from a desirable steady state. The resulting stasis enables organisms to function reliably while being subjected to very different external environments. This perspective concerns a stringent type of biological adaptation, robust perfect adaptation (RPA), that is resilient to certain network and parameter perturbations. As in engineered control systems, RPA requires that the regulating network satisfy certain structural constraints that cannot be avoided. We elucidate these ideas using biological examples from systems and synthetic biology. We then argue that understanding the structural constraints underlying RPA allows us to look past implementation details and offers a compelling means to unravel regulatory biological complexity.
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