We often think of its units, the As, Cs, Ts, and Gs, as letters of the words in an instruction manual.
While realizing this new concept of molecular recording, Shipman together with second-author Jeff Nivala, a research fellow in genetics at HMS, identified a valuable set of requirements in their analysis that make spacer sequences likely to be more easily acquired and defined sequence features that prevent their acquisition into growing CRISPR arrays-the do's and don'ts of spacer design. Here, in a structural analysis, Jiyung Shin et al. first examined how the natural inhibitor protein AcrIIA4 interacts with the Cas9 enzyme.
The technical achievement, reported on July 12 in Nature, is a step towards creating cellular recording systems that are capable of encoding a series of events, says Seth Shipman, a synthetic biologist at Harvard Medical School in Boston, Massachusetts. Near the CRISPR section of the genome are genes that code for a family of enzymes called Cas, whose job is to slice through DNA strands.
The team included researchers in the lab of Jennifer Doudna, one of the inventors of CRISPR-Cas9 gene editing, who determined how the anti-CRISPR protein binds to the CRISPR-Cas9 complex.
While this new technology could be used for many things, the research team hopes that it will allow them to study the human brain. What stops scientists from harnessing the power of those units, using the latest biological technology to treat DNA like a writable disk? The information was stretched across the genomes of numerous bacteria instead of just one.
To accomplish this feat, the first of its kind, the researchers started with five frames from a classic 1870s movie of a racehorse.
The researchers then employed the Crispr platform, in which two proteins are used to insert genetic code into the DNA of target cells - in this case, those of E.coli bacteria.
According to Shipman, the sequential nature of CRISPR makes it an appealing system for recording events over time.
If this ability could be naturally turned on and enabled to register other types of data, scientists believe they could be able to track, monitor or predict disease or health dangers in real time. However, they would ultimately like to use it to study the brain. Considering the initial discoveries of anti-CRISPR proteins were only published last December, he says, these studies were conducted at an incredibly rapid pace.
The team used still and moving images because they represented constrained and clearly defined data sets; the movie also gave the bacteria a chance to acquire information frame by frame. "It's compact, and it's incredibly stable".
Shipman told the BBC the team wanted to eventually use the technique to create "molecular recorders". When a bacterium is infected by a virus, parts of the foreign DNA is cut out by CRISPR, which then gets stored in the bacteria's own genome.
They managed to encode a GIF file into the cells of a living bacteria, an E. coli, and then reconstructed and played it back. "It's much more stable than silicon memory if you wanted to hold something for thousands of years".
So the group converted the image and movie into short DNA segments that look like fragments of viruses, and, frame by frame, introduced them to the organism.
The image of a human hand (left) was encoded into bacterial DNA and then extracted (right) after several generations of bacterial growth.