Researchers create world's smallest tape recorder from gut bacteria

Researchers have modified a strain of human gut bacteria, to create what is essentially the world's smallest data recorder.

The biologically engineered bacteria are capable of recording their interactions with the surrounding environment and even time-stamp events, which will allow for the development of new technologies that harness bacterial cells for purposes ranging from disease diagnosis to environmental monitoring. These cells can 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," said Harris Wang, assistant professor at Columbia University Medical Center and senior author of the new research in a press release.

In order to teach the bacteria known as Escherichia coli the data-recording ability, the scientists harnessed the power of their inbuilt immune system, known as CRISPR-Cas. When viruses infect these bacteria, this immune system copies snippets of DNA from the invading pathogens to allow subsequent generations to repel and destroy them more effectively.

The CRISPR-Cas system, in essence, creates a chronological record of all the viruses that have infected the bacteria and their ancestors.

Columbia University said in a press release, ''Wang and members of his laboratory created the microscopic data recorder by taking advantage of CRISPR-Cas, an immune system in many species of bacteria. CRISPR-Cas copies snippets of DNA from invading viruses so that subsequent generations of bacteria can repel these pathogens more effectively. As a result, the CRISPR locus of the bacterial genome accumulates a chronological record of the bacterial viruses that it and its ancestors have survived. When those same viruses try to infect again, the CRISPR-Cas system can recognize and eliminate them.

''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.''

CRISPR-Cas normally uses its recorded sequences to detect and cut the DNA of incoming phages. The specificity of this DNA cutting activity has made CRISPR-Cas the darling of gene therapy researchers, who have modified it to make precise changes in the genomes of cultured cells, laboratory animals, and even humans. Indeed, over a dozen clinical trials are now underway to treat various diseases through CRISPR-Cas gene therapy.

But Ravi Sheth, a graduate student in Wang's laboratory, saw unrealised potential in CRISPR-Cas's recording function. ''When you think about recording temporally changing signals with electronics, or an audio recording that's a very powerful technology, but we were thinking how can you scale this to living cells themselves?'' says Sheth.

To build their microscopic recorder, Sheth and other members of the Wang lab modified a piece of DNA called a plasmid, giving it the ability to create more copies of itself in the bacterial cell in response to an external signal.

A separate recording plasmid, which drives the recorder and marks time, expresses components of the CRISPR-Cas system.

In the absence of an external signal, only the recording plasmid is active, and the cell adds copies of a spacer sequence to the CRISPR locus in its genome.

When an external signal is detected by the cell, the other plasmid is also activated, leading to insertion of its sequences instead. The result is a mixture of background sequences that record time and signal sequences that change depending on the cell's environment. The researchers can then examine the bacterial CRISPR locus and use computational tools to read the recording and its timing.

The current paper proves the system can handle at least three simultaneous signals and record for days.

''Now we're planning to look at various markers that might be altered under changes in natural or disease states, in the gastrointestinal system or elsewhere,'' says Dr. Wang.

Synthetic biologists have previously used CRISPR to store poems, books, and images in DNA, but this is the first time CRISPR has been used to record cellular activity and the timing of those events.''