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Depending on how they’re designed, production of the RNA switches can be regulated by exposing the bacteria to a particular chemical. By controlling how much of the “on” and “off” RNAs are made, it’s also possible to regulate protein production over a continuum, not just turn it totally on or off.

While other gene-expression techniques need to be engineered for a particular gene, Collins says, the RNA-based switch “can be used to control any gene of interest.” Other switches rely on proteins to regulate gene expression. But the use of proteins requires several steps, which means they’re not as fast to make as the RNA switches.

The microbial self-destruction system Collins made to demonstrate the switches uses two genes that, when expressed at the same time, create two proteins that cause the cell to burst. Both genes are set to “off” in all cells by the ribosome-binding RNA component until an external chemical stimulus causes the cells to produce the second piece of RNA, freeing up the ribosome to make the cell-killing proteins.

Such a kill switch could be useful in microbes designed to, for example, break down environmental toxins. Once the microbes have cleaned up a toxin, “you could spray the area with an innocent compound that triggers cells to expire on command,” says Collins. The kill switch could also be coupled to other synthetic biology tools such as genetic clocks in order to design bacteria that live for a given number of days.

These switches make it possible “to do the kinds of things people like me struggle to do,” says Robertson. One of the main challenges for a company like Joule, he says, is complying with regulations about environmental containment of genetically modified organisms, and Collins’s switch could help.

Collins is currently working to combine the switches to make what he calls tunable “switchboards.” “We want to tune genes like a rheostat,” he says. Such a switchboard might be used to control a population of cells so that they first put their energies toward growing their population. Then, when engineers deem it timely, they can administer chemical signals that cause the cells to gradually ramp up production of a fuel, for example.

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Credit: PNAS

Tagged: Biomedicine, DNA, genetics, genetic engineering, synthetic biology, RNA, microbes, gene expression

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