We used a model system of purified components to explore the effects of a downstream target on the signaling properties of a covalent modification cycle, an example of retroactivity. In the experimental system used, a bifunctional enzyme catalyzed the modification and demodification of its substrate protein, with both activities regulated by a small molecule stimulus. Here we examined how a dow...

Retroactivity arises when the coupling of a molecular network U to a downstream network D results in signal propagation back from D to U . The phenomenon represents a breakdown in modularity of biochemical circuits and hampers the rational design of complex functional networks. Considering simple models of signal-transduction architectures, we demonstrate the strong dependence of retroactivity ...

Modularity is a property by which the behavior of a system does not change upon interconnection. It is crucial for understanding the behavior of a complex system from the behavior of the composing subsystems. Whether modularity holds in biology is an intriguing and largely debated question. In this paper, we discuss this question taking a control system theory view and focusing on signaling sys...

Synthetic biology is a bottom-up engineering discipline: modules are systematically designed with predefined behavior and then combined to build up larger biomolecular circuits. Although the modules produce the desired behavior in isolation, they fail to operate properly when they are connected due to retroactivity, an effect which extends the notion of impedance to biomolecular systems. Despit...

In public health, because of our commitment to advocacy, there is always the danger of becoming a believer — becoming so convinced about the issues one is pursuing that it becomes difficult to consider new information objectively. Although a degree of subjectivity is inherent in all scientific inquiry, one who believes uncritically risks missing opportunities to progress based on new insights, ...