DNA is the primary information storage medium in all living organisms and can be harnessed to act as synthetic cellular memory devices, one such DNA-based system harnessed for many different uses is CRISPR. CRISPR, a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea, has been developed into a technology that can be used to edit genes within cells. As this editing system works on the nanoscale, it is thought to contain the potential for limitless applications. Now, a study from researchers at Columbia University uses CRISPR to convert a natural bacterial immune system into a microscopic data recorder. The team states their study lays the groundwork for a new class of technologies using bacterial cells for everything from disease diagnosis to environmental monitoring. The study is published in the journal Science.
Previous studies show CRISPR or 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 using CRISPR-Cas gene therapy. The current study modifies an ordinary laboratory strain of the ubiquitous human gut microbe Escherichia coli, enabling the bacteria to record their interactions with the environment and time-stamp the events.
The current study modifies 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, to build their microscopic recorder. Results show a separate recording plasmid expressing components of the CRISPR-Cas system drives the recorder and marks time. Data findings show in the absence of an external signal only the recording plasmid is active, meaning the cell only adds copies of a spacer sequence to the CRISPR locus in its genome.
The team explains when an external signal is detected by the cell, the other plasmid is also activated, leading to the insertion of its sequence instead. They go on to add the result is a mixture of background sequences recording time and changing signal sequences dependent on the cell’s environment. They conclude it is then possible to examine the bacterial CRISPR locus and use computational tools to read the recording with its time stamps.
The team surmises they have developed a microscopic data recorder by taking advantage of CRISPR-Cas. For the future, the researchers state they’re planning to look at various markers affected by changes to the environment in the gastrointestinal system or elsewhere.
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