Bacteria in Green are On, Red Bacteria are Off  (Source: Lingchong You)
Researchers discover bistability in genetically altered E.coli used in synthetic circuit

Scientists are conducting research into creating synthetic circuits using genetically altered bacteria. The goal is to allow these bacteria to create a type of living circuit to produce proteins that are useful inside the body for treating conditions and diseases like cancer.

Researchers Lingchong You and graduate student Cheemeng Tan have designed a set of experiments on a living circuit created using genetically altered E.coli bacteria that has demonstrated the existence of "bistability" in bacteria cells. This bistability makes some bacteria in the synthetic circuit act differently than the other bacteria when stimulated in the same way.

According to the researchers, taking this ability for the bacteria to act differently inside the circuit can greatly enhance the efficiency of synthetic circuits. Synthetic circuits are being eyed for use in treating disease conditions to produce proteins, enzymes, or chemicals in a coordinated way. The circuits could also be used to deliver drugs or selectively kill cancer cells according to the researchers.

The genetically altered bacteria used in synthetic biology are altered to direct their actions in a way that a software program directs a computer. The experiments by You and Tan have shown that the genetic alteration (the software) can also influence the bacteria (the computer).

"In the past, synthetic biologists have often assumed that the components of the circuit would act in a predictable fashion every time and that the cells carrying the circuit would just serve as a passive reactor," You said. "In essence, they have taken a circuit-centric view for the design and optimization process. This notion is helpful in making the design process more convenient."

"We found that there can be unintended consequences that haven't been appreciated before," said You. "In a population of identical cells, some can act one way while others act in another. However, this process appears to occur in a predictable manner, which allows us to take into account this effect when we design circuits."

Electrical engineers have to deal with bistability as well and in engineering, the term describes the functioning of a toggle switch that can be on or off. During the experiments conducted by the pair of researchers, they found that the stimulation that turned the majority of the colony of E.coli on, making them grow more slowly, also turned some of the bacteria off making them grow faster.

"It is as if the colony received the command not to expand too fast when the circuit is on," Tan explained. "Now that we know that this occurs, we used computer modeling to predict how many of the cells will go to the 'on' or 'off' state, which turns out to be consistent with experimental measurements"

The researchers believe that the discovery can aid scientists and researchers in building more efficient synthetic circuits in the future.

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