Holy Don Quixote...the intelligence and humor of CRISPR.

Movie buffs may recognize the image of the galloping horse from the first moving picture credited to Eadweard Muybridge (although often debated).

Click the link for more details including his trial for the murder of his wife's lover--oh yes. Who says science isn't interesting?

In an act of brilliant thread pulling, this was the image recently reproduced by CRISPR-Cas technology. You may have seen the images and thought, "wow that is cool". Me too. 

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How do you encode new genetic information into a genome? I am helluva interested in the CRISPR-Cas molecular recording. First a little background to help level set the conversation. Clustered regularly interspaced short palindromic repeats or CRISPR are a type of bacterial genetic memory containing repeating sequences of genetic code interrupted by remnants of code called "spacer" sequences. Spacer sequences are actually viral DNA molecules from previous infections. These sequences are characteristic of the bacterial defense system and serve as the basis for genome editing technology.

Briefly and perhaps a bit too simplistically, these “spacer” sequences are transcribed into short RNA sequences looking to match sequences of DNA. When the target DNA is found, an enzyme produced by the CRISPR system – binds to the DNA and cuts it, shutting the targeted gene off.The natural repair mechanisms of the cell can now introduce mutations or other changes to the genome. Although a remarkable improvement over previous gene editing tools--CRISPR may cause off-target effects and imprecise edits.

Shipman and colleagues engineered Cas 1 and Cas 2, two proteins of the CRISPR system. The digital memories were deposited into the genome in a similar way as cellular immunity. The movie represented the acquisition of information frame by frame. The CRISPR–Cas system encoded pixel values of a black and white short movie into the genomes of a population of living bacteria.

“We designed strategies that essentially translate the digital information contained in each pixel of an image or frame as well as the frame number into a DNA code, that, with additional sequences, is incorporated into spacers. Each frame thus becomes a collection of spacers,” --Seth L. Shipman

“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. And after retrieving all arrays again from the bacterial population by DNA sequencing, we finally were able to reconstruct all frames of the galloping horse movie and the order they appeared in.”--Seth L. Shipman

CRISPR-Cas encoding of a digital movie into the genomes of a population of living bacteria
Shipman, Nivala, Macklis, Churchdoi:10.1038/nature23017

Shipman and his research team from Wyss Institute for Biologically Inspired Engineering and Harvard Medical School coerced living cells into using their genomes as a biologic hard drive of sorts.

A recent study published in Nature evolved their research and encoded a sequence of a galloping horse into living cells. 

​You can see the first frame depicted in the image with the corresponding  pixel set (pixels 1 -9) and genetic sequence.

​Figure D from journal article shows the biologic replicates in the order necessary to help with reconstruction of image.

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“...without intelligence, there can be no humour.” 
― Miguel de Cervantes Saavedra, Don Quixote

There are days when science is amazing. In fact, aren't most days like that?