A team of scientists from Massachusetts Institute of Technology has developed a technique for creating living gene circuits that are capable of performing complex computations.

Such computations are essential for receiving and processing biological signals. Current computation methods are exclusively either analog or digital in nature.

Analog computation, also known as continuous computation, usually occurs when the eye adjusts to light conditions.

On the other hand, digital computation comprises of binary decision making or on or off processes. One example is a cell's initiation of its own death.

Indeed, typical synthetic biological systems can only be either analog or digital, limiting the applications in which they can be used.

Combining Complex Computations

Now, however, the team's newly designed gene circuit is much better: it can do both of these complex computations.

How so? Researchers say the circuitry acts like a comparator -- a device that typically compares two currents and outputs. It receives analog signals for input, and then converts them into digital signals as an output.

In this case, the circuitry is capable of measuring the level of analog inputs -- such as a particular chemical relevant to a disease -- and deciding whether this level is the right range to turn on an output. The output may be a drug that combats the disease.

Associate Professor Timothy Lu, one of the lead researchers of the study, says most of the work in synthetic biology focuses on the digital approach because it is much easier to program.

But because these digital processes greatly rely on binary output of either 0 or 1, complex computational operations require the use of large numbers in parts. That would be difficult to achieve with current methods.

Lu says the digital approach also involves producing something intelligent out of very simple parts. Each part performs a simple process, but when you combine them, the product is "smart."

The challenge in biology is one cannot assemble billions of "transistors" the same way engineers do on a piece of silicon, he says.

Converting Input Into Output

The device that Lu and his colleagues have created is based on several elements. It contains a threshold module with a sensor that senses analog levels of a chemical.

The threshold module can control the expression of another component: a recombinase gene. This gene can switch on or off a DNA segment by means of inversion. This converts the analog signal into digital.

"Once that is done, you have a piece of DNA that can be flipped upside down," says Lu. "Then you can put together any of those pieces of DNA to perform digital computing."

Lu and his team have already developed an analog-to-digital converter circuit that applies ternary logic. This will only switch on as a response to either a low or high concentration of an input.

Applications Of The Gene Circuit

In the future, the gene circuit could be applied to detect blood glucose levels and respond depending on the level of concentration found.

Lu says if the glucose levels were too high, the cells would produce insulin. If the glucose levels were too low, the cells would make glucagon. However, if the glucose levels were normal, the cells wouldn't do anything.

The research team began a spinout company named Synlogic, which attempts to use the circuit to develop probiotic bacteria that can treat disease in the gut.

The circuitry could also be potentially used in cancer treatment, which will be engineered to detect different environment inputs. The response output would vary.

Additionally, Lu says other scientists are interested in using the synthetic process in detecting concentrations of water pollutants.

The details of the study are issued in the journal Nature Communications.

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