The world’s smallest tape recorder is built from microbes.
While dynamics underlie many biological processes, the global medical community’s ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Now, a study from researchers at Columbia University converts a natural bacterial immune system into a microscopic data recorder. The team state that their study lays the groundwork for a new class of technologies which use bacterial cells for everything from disease diagnosis to environmental monitoring. The study is published in the journal Science.
Previous studies show that 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. The current study modifies an ordinary laboratory strain of the ubiquitous human gut microbe Escherichia coli, which enables 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 that a separate recording plasmid, which drives the recorder and marks time, expresses components of the CRISPR-Cas system. Data findings show that 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.
The team explain that when an external signal is detected by the cell, the other plasmid is also activated, leading to insertion of its sequences instead. They go on to add that the result is a mixture of background sequences that record time and signal sequences that change depending on the cell’s environment; the current study proves the system can handle at least three simultaneous signals and record for days. They conclude that it is then possible to examine the bacterial CRISPR locus and use computational tools to read the recording and its timing.
The team surmise that they have developed a microscopic data recorder by taking advantage of CRISPR-Cas, an immune system in many species of bacteria. For the future, the researchers state that they’re planning to look at various markers that might be altered under changes in natural or disease states, in the gastrointestinal system or elsewhere.