By responding to chemical changes in the environment and then ‘time-stamping’ them in DNA, the technology paves the way for living monitoring devices that could be utilized in health screens or to analyze pollutants in ecosystems.
Scientists from the Columbia University Medical Center in the US co-opted the gene editing system known as CRISPR-Cas from the bacterium Escherichia coli, taking advantage of its natural ability to remember the genetic information of viruses.
“From an engineering standpoint that is actually quite nice, because it’s already a system that has been honed through development to be really great at storing information.”
CRISPR is in fact the gift that just keeps giving. Few technologies have the right to be called revolutionary, but thanks to its relative simplicity and reliability, the molecular system has already made its mark altering the area of genetic engineering.
The tool functions based on a principle we’ve observed in bacteria – as it happens, a bacterium such as E. coli comprises ‘libraries’ of genetic sequences which allow it to identify invasive viruses.
The bacterium copies these libraries onto sections of RNA that helps enzymes known as Cas to quickly recognize viral genomes and rip them up before they can cause damage.
This is what makes the system incredibly useful as a molecular scalpel. But in this instance, the researchers turned their attention to the library itself.
“When you think about recording temporally changing signs with electronics, or an audio recording … that’s a really powerful technology, but we were thinking how do you scale this to living cells themselves?” Says among Wang’s graduate students, Ravi Sheth.
The team used circular pieces of DNA called plasmids as the messages in the data library.
By triggering the creation of specific messages in response to a particular signal — like the presence of a metabolite like copper or the sugar fucose — the scientists were able to record a specific environmental change. These changes in a sequence that could be interpreted as a measure of time.
That is where CRISPR comes in. Machinery was tweaked to answer the amount of these plasmids by stitching them into a sequence, much like a tape recorder.
When there was a lack of plasmids, the machines continued to construct the sequence using another kind of plasmid as a benchmark spacer; kind of the equivalent of dead air.
The mix of plasmids provides a timestamp for when changes in the environment occur.
“This approach enables stable recording over several days and the team calls their technology ‘temporal recording in arrays by CRISPR expansion’, or TRACE for short.
The next step for TRACE is to respond to disease biomarkers from the digestive system that could fluctuate over a few days.
With growing piles of evidence linking gut microbes with many different conditions, from Parkinson’s into chronic fatigue into multiple sclerosis, having sharper tools for analyzing the intricate environments inside us is a no-brainer. Changes they experience through the whole digestive tract, yielding an unprecedented view of formerly inaccessible phenomena,” says Wang.