Retroactivity and Insulation

A central concept in synthetic biology is the construction of reusable, well-characterized modules. Modularity simplifies circuit design by allowing engineers to decouple systems into separate modules and construct and test modules individually. Instead of designing genetic circuits from scratch with each project, complex regulatory networks can be quickly assembled from a library of functional devices. Characterization of external module behavior, such as with input/output signal response curves, provides a useful abstraction that does not require a biological engineer to know about internal device workings.

Modularity is an existing and essential concept in engineering fields such as electrical engineering and computer architecture, and this abstraction can be applied to synthetic biology. However, current devices constructed in synthetic biology may not actually exhibit modular behavior. Modularity fails when individual device behavior depends on the behavior of other connected components. In particular, device characteristics may change upon different interconnections, a phenomenon called retroactivity.

Retroactivity is undesirable in biological engineering, as it decreases the reliability and predictability of device behavior in different circuit settings. Every time a new component is added to a system, new connections are made which can affect input/output characteristics of all of the devices in the system. Therefore, iterative redesign of the network might be necessary to accommodate each new change, which is time-consuming and inefficient. Ideally, modules should function similarly whether tested individually or placed into larger systems. This project seeks to experimentally verify that retroactivity affects connections between modules in vivo and to demonstrate that a genetic insulator can be placed in between modules to buffer against retroactivity.