The microscopic world inside our bodies can be pretty mysterious, but researchers from Columbia University have developed a technique that lets them send a spy in to see what's going on in there. The process is to essentially "bug" a bug, where bacteria are engineered to record what they interact with on their journey through the gastrointestinal tract, and even timestamp when those events occurred.
Rather than build their microbial "tape recorder" from scratch, the researchers adapted a natural system that already functions in a similar way. CRISPR-Cas is a kind of immune system used by many species of bacteria, and it works a bit like a Wanted poster: essentially, whenever a bacteria survives an encounter with a bacteriophage (a virus that attacks bacteria), CRISPR-Cas copies a snippet of the invader's DNA. That way, if that species reappears down the track, even generations later, the bacteria can recognize it and fight back.
If CRISPR sounds familiar, that's because its DNA-snipping prowess makes it a great gene editing tool, and scientists around the world are currently experimenting with it as a way to treat a whole host of illnesses, from HIV to cancer.
"The CRISPR-Cas system is a natural biological memory device," says Harris Wang, senior author of the study. "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."
Working with the bacteria E. coli, the researchers began by modifying short fragments of DNA called plasmids, for two different functions. One plasmid was made to act as a kind of timekeeper, regularly copying a spacer sequence to the CRISPR site in the bacteria's genome, while a second was designed to copy itself only when the bacteria detected a specific external signal. That way, the timing of a signal can be determined by looking at the amount of spacer sequences before and after the signal.
In practice, these engineered bacteria could be recruited to trek through a patient's body in search of specific stimuli, like viruses, that might be causing an illness.
"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 Wang. "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."
In their tests, the Columbia team found that the system could keep the recording running for days at a time, and keep watch for three different signals simultaneously. And the technique wouldn't just be limited to the human microbiome, as these spies could help check waterways or other environments for pathogens.
The research was published in the journal Science.
Source: Columbia University