Complex, reliable and modular synthetic biology networks will enable biosensing cancer and other applications

Individual biological circuit componentss can have precise and predictable responses but those outcomes become less predictable as more such elements are combined.

A team of researchers at MIT has now come up with a way of greatly reducing that unpredictability, introducing a device that could ultimately allow such circuits to behave nearly as predictably as their electronic counterparts.

There are many potential uses for such synthetic biological circuits, Del Vecchio and Weiss explain. “One specific one we’re working on is biosensing — cells that can detect specific molecules in the environment and produce a specific output in response,” Del Vecchio says. One example: cells that could detect markers that indicate the presence of cancer cells, and then trigger the release of molecules targeted to kill those cells.

It is important for such circuits to be able to discriminate accurately between cancerous and noncancerous cells, so they don’t unleash their killing power in the wrong places, Weiss says. To do that, robust information-processing circuits created from biological elements within a cell become “highly critical,” Weiss says.

Nature Biotechnology – A load driver device for engineering modularity in biological networks

The device the team produced to address that problem is called a load driver, and its effect is similar to that of load drivers used in electronic circuits: It provides a kind of buffer between the signal and the output, preventing the effects of the signaling from backing up through the system and causing delays in outputs.

While this is relatively early-stage research that could take years to reach commercial application, the concept could have a wide variety of applications, the researchers say. For example, it could lead to synthetic biological circuits that constantly measure glucose levels in the blood of diabetic patients, automatically triggering the release of insulin when it is needed.

Abstract

The behavior of gene modules in complex synthetic circuits is often unpredictable. After joining modules to create a circuit, downstream elements (such as binding sites for a regulatory protein) apply a load to upstream modules that can negatively affect circuit function. Here we devised a genetic device named a load driver that mitigates the impact of load on circuit function, and we demonstrate its behavior in Saccharomyces cerevisiae. The load driver implements the design principle of timescale separation: inclusion of the load driver’s fast phosphotransfer processes restores the capability of a slower transcriptional circuit to respond to time-varying input signals even in the presence of substantial load. Without the load driver, we observed circuit behavior that suffered from a 76% delay in response time and a 25% decrease in system bandwidth due to load. With the addition of a load driver, circuit performance was almost completely restored. Load drivers will serve as fundamental building blocks in the creation of complex, higher-level genetic circuits.

58 pages of supplemental material

SOURCES – MIT, Nature Biotechnology

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