Researchers at Columbia University Medical Center have modified bacterial immune system of human gut microbe Escherichia coli, enabling the bacteria to not only record their interactions with the environment but also time-stamp the events. They have turned bacteria into a microscopic data recorder, creating groundwork for a new class of technologies that could use bacterial cells for multiple uses like disease diagnosis to environmental monitoring.
Wang and members of his laboratory created this technology by taking advantage of CRISPR-Cas. 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. CRISPR-Cas normally uses its recorded sequences to detect and cut the DNA of incoming phages.
To build their microscopic recorder, Ravi 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.
Citation: Sheth, Ravi U., Sung Sun Yim, Felix L. Wu, and Harris H. Wang. “Multiplex recording of cellular events over time on CRISPR biological tape.” Science, 2017.
Funding: US Department of Defense, National Institutes of Health, Sloan Foundation.
Adapted from press release by Columbia University Medical Center.