Gene Circuits Can Now Perform Complex Non-Binary Operations

Cells have long been known to perform complicated computations via various “on/off” switching behaviour – allowing them to signal to one another about their environment and internal states. The computations can be either continuous in nature, digital or analogue. Digital computations result in the familiar “on off” model like in circuits.

Until now, the digital method has been the most commonly used in synthetic biology, which has limited the applications of cells to similar logical functions as computers. But now that is about to change. A team of scientists at MIT developed a method to combine both digital and analogue computations together within cells, forming circuits composed of genes that are capable of carrying out complicated operations.

The researches published their paper and showed that their cells were able to monitor the actual levels of various biochemicals (analogue behaviour) and, depending upon the concentration, send out logical signals more familiar in digital circuits. The applications are immense, as the detection of biochemicals that are indicative of a disease could give these cells an ability to communicate early warning signs. The technique could also be used to give feedback whether a drug is working to treat a disease, and how much dosage is required.

According to the scientist who led the research; Timothy Lu, associate professor of EE. at MIT’s Synthetic Biology Group, the cells act similar to devices known as “comparators”. Comparators receive analogue inputs and convert them into a digital output signal.  “Most of the work in synthetic biology has focused on the digital approach, because digital systems are much easier to program,” says Lu. The drawback of this of course is that the output can only be in the form of a 0 or 1, an “on” or an off”. Whilst good for a computer, this greatly limits complex calculations in biology that involve responding to the environment.

The new mixed analogue/digital device that the researchers created is complex. One of its modules contains a sensor that detects analogue concentrations of biochemicals. Once a threshold is reached, a signal is sent to another component called a “recombinase gene”. This gene can then turn a segment of DNA either on or off by binding to it.

Planned applications for this new technology include the monitoring of glucose levels in the bloodstream. The analogue part of the technology could be used to monitor the concentration of glucose, and if it was found to be too high, a simple digital output could signal other cells to produce insulin, Likewise, if the concentration were too low, the output could trigger production of glucagon.

Already the researchers have formed a new company called Synlogic which is now looking to use basic implementations of this dual-function biocircuit to produce probiotics that target diseases in the gut. Clinical trials are expected within the year.

Source: MIT News

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