Movie encoded in DNA in first step to 'molecular recorders,' scientists say

How the protein AcrIIA4 affects Cas9.    
   Illustration Shin et al. Sci. Adv. 2017;3 e1701620

How the protein AcrIIA4 affects Cas9. Illustration Shin et al. Sci. Adv. 2017;3 e1701620

Bacteria already use the "Cas" proteins associated with CRISPR to grab pieces of DNA from viruses and insert it into their genomes as a defence mechanism against future attacks. The team decided to hack this system for their own purposes, says study co-author Seth Shipman, a neuroscience researcher at Harvard University. So we used static images and then we used moving images which we delivered over time to living bacteria, and then we were able to sequence those bacteria and reconstruct the image.

Harvard University researchers, which are behind the new study, state that they want to "turn cells into historians". At right are the frames recovered by sequencing bacterial genomes, after multiple generations of bacterial growth.

"We can use that to generate what we call molecular records, or recordings, into the genome of a living bacteria".

The bacterial system they used to accomplish this mind-bending feat is nothing short of remarkable.

Thus this "anti-CRISPR DNA mimic" could be the saviour of CRISPR as a remedial therapy, with the inhibitor "broadly useful in situations where precise control of either on- or off-target gene editing is desirable". We often think of its units, the As, Cs, Ts, and Gs, as letters of the words in an instruction manual. "These could be used to model disease - or even in therapies".

"What this shows us is that we can get the information in, we can get the information out, and we can understand how the timing works, too", Shipman said. The Crispr-Cas9 is a molecular tool that combines RNA molecules and special proteins to precisely cut and edit DNA. And this GIF-only 36 by 26 pixels in size-represents a relatively small amount of information compared to what scientists have so far been able to encode in synthetic DNA.

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Instead of sending out Cas enzymes to chop up distant places in the genome, Shipman's group let the CRISPR system behave like it normally does: as a mechanism for grabbing viral DNA and bringing it home to the CRISPR section of the genome. George Church and Jeffrey Macklis to transfer the encoded DNA into the bacteria. "We then provided spacer collections for consecutive frames chronologically to a population of bacteria which, using Cas1/Cas2 activity, added them to the CRISPR arrays in their genomes".

CRISPR was also used to encode this image of a hand into a bacterial genome. They sequentially treated bacteria with a frame of translated DNA over the course of five days. After looking at the genome of the new cells, researchers found the synthetic DNA containing the trotting horse was in the genetic code with 90% accuracy.

Ultimately, the same technology that today is being demonstrated with vintage images of a galloping horse could be used to unlock one of the great remaining mysteries of human biology: the workings of the brain.

"We want to use neurons to record a molecular history of the brain through development", said Shipman.

"Such a 'molecular recorder' will allow us to eventually collect data from every cell in the brain at once, without the need to gain access, to observe the cells directly, or disrupt the system to extract genetic material or proteins". Shipman et al, doi: 10.1038/nature23017.

The Harvard team also sequenced the image of a hand onto biological DNA and then retrieved it. The currently technology, however, required Shipman's team to manually enter the information. "Each frame thus becomes a collection of spacers", said Shipman, the study's first author.

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