World’s smallest ‘tape’ recorder uses hacked microbes
Using “molecular hacks,” the researchers were able to modify an ordinary laboratory strain of bacteria commonly found in the human gut to not only record their interactions with the environment but to also “time-stamp” the events. This, say the researchers, could lay the groundwork for a new class of technologies that use bacterial cells for everything from disease diagnosis to environmental sensing – anyplace.where bacteria could monitor otherwise invisible changes without disrupting their surroundings.
“Such bacteria, swallowed by a patient, might be able to record the changes they experience through the whole digestive tract, yielding an unprecedented view of previously inaccessible phenomena,” says Harris Wang, assistant professor in the Departments of Pathology & Cell Biology and Systems Biology at CUMC and senior author of a paper describing the work.
To achieve their result, the researchers exploited an immune system found in many species of bacteria, called CRISPR-Cas, which copies snippets of DNA from invading viruses to enable subsequent generations of bacteria to recognize and repel these pathogens more effectively in the future. In doing so, it accumulates a chronological record of the bacterial viruses that it and its ancestors have survived.
“The CRISPR-Cas system is a natural biological memory device,” says Wang. “From an engineering perspective that’s actually quite nice, because it’s already a system that has been honed through evolution to be really great at storing information.”
To create their data recorder, the researchers modified a piece of DNA called a plasmid to give it the ability to create more copies of itself in the bacterial cell in response to an external signal. A second, separate recording plasmid drives the recorder and marks time.
When there is no external signal, only the recording plasmid is active, and the cell adds copies of a blank spacer sequence to the CRISPR locus in its genome. However, when an external signal is detected, the other plasmid is also activated, leading to insertion of its sequences instead.
The result, say the researchers, is a mixture of background sequences that record time and signal sequences that change depending on the cell’s environment. According to the researchers, the system can handle at least three simultaneous signals and record for days. This information can then be examined by the researchers using computational tools to read the recording and its timing.
While CRISPR has been previously used to store various data in DNA, say the researchers, this is the first time it has been used to record cellular activity and the timing of those events. They are now planning to look at various markers that might be altered under changes in natural or disease states, in the gastrointestinal system or elsewhere.
For more, see “Multiplex recording of cellular events over time on CRISPR biological tape.”
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