Researchers Create Most Complex Synthetic Circuit Ever
October 9, 2012

Researchers Create Most Complex Synthetic Circuit Ever

Lee Rannals for — Your Universe Online

MIT researchers have developed circuit components that can produce the most complex synthetic circuit ever built.

The circuit, which was reported in the journal Nature, integrates four sensors for different molecules, and can be used in cells to precisely monitor their environment and respond appropriately.

The team had previously designed bacteria that could respond to light and capture photographic images, and others that can detect low oxygen levels and high cell density. However, Christopher Voigt, an associate professor of biological engineering at MIT, said that they were just repackaging the same circuits over and over again.

In order to expand the number of possible circuits, the team needed components that would not interfere with each other, so they started to study the bacterium that causes salmonella.

The team found 60 different versions of a pathway that consists of an activator, a promoter and a chaperone in other species of bacteria. They also found that most of the proteins in each were different enough that they did not interfere with one another.

They used an approach called directed evolution to help reduce it, which is a trial-and-error process that involves mutating a gene to create thousands of similar variants.

“A lot of people are charmed by the idea of creating complex genetic circuits," Aindrila Mukhopadhyay, a staff scientist at Lawrence Berkeley National Laboratory (LBL) who was not a part of the research, said in a press release. "This study provides valuable examples of the types of optimizations that they may have to do in order to accomplish such goals."

In order to design synthetic circuits so they can be layered together, their inputs and outputs must mesh. With these biological circuits, the inputs and outputs are protein that control the next circuit.

“The cell is sort of a burrito. It has everything mixed together,” Voigt said. “It´s incredibly complex, stitching together all these pieces."

These components could be useful for creating circuits that can sense a variety of environmental conditions.

“If a cell needs to find the right microenvironment – glucose, pH, temperature and osmolarity [solute concentration] – individually they´re not very specific, but getting all four of those things really narrows it down,” Voigt said in a press release.

The team is now going to apply their research to create a sensor that will allow yeast in an industrial fermentor to monitor their own environment and adjust their output accordingly.