Roll the tape! CRISPR technology directs new sci-fi blockbuster

And no. It isn’t a GATTACA revival.

If you haven’t heard, the CRISPR revolution is among us. This powerful gene-editing tool can manipulate DNA; the fundamental code to life everywhere. Just this year, we’ve seen it behind creating organ donor piglets, discovering butterfly wing patterns, and making a controversial edit within a human embryo,

Now, we’re exploring another side to CRISPR: cellular memory.

The ability to rewind and replay key decisions made by a growing cell would revolutionise developmental biology. Achieving it in a non-invasive way is the aim of Harvard University researchers who’ve turned their bacterial colonies into little CRISPR movie makers, dreaming of making it big on the silver screen. The bacteria acted like live thumb-drives, and passed the film on for generations before the researchers decoded it.

If you gave a cell a GoPro, would it record adrenaline-fuelled cellular activity? Source: Jeremy Yap on Unsplash. Image has been cropped.

 

Act 1: The Hero’s Journey 

Big things can come from small beginnings in genetics. Bacteria, facing harsh environments where they are outnumbered ten-to-one by viral invaders, need something to defend themselves. This is where CRISPR-Cas is equipped – a bacterial adaptive immune system.

Upon infection by a virus, the CRISPR-Cas system captures a fragment of the viral genome. It then inserts the fragment into the beginning of a “CRISPR array” sequence within the bacterial genome. If another type of virus invades, their fragment fingerprints will be added to the next file in the CRISPR array database.

It may seem counterintuitive to store parts of your enemies. But the array sequence prints out wanted posters of these viral perps like a ten-year old using a copy machine unsupervised. These posters then get distributed to the ‘Cas9’ sheriffs who police every corner of the cell, watching and waiting to remove the invaders quicker next time.

Act 2: A Trusty Steed 

The Harvard research team wanted to test the ordered way foreign sequence data is remembered in bacteria, and then show that it could be decoded. They chose to encode a five-frame, 36 x 26 pixel, version of Eadweard Muybridge’s famous galloping mare and rider from his Human and Animal Locomotion series.

Eadweard Muybridge’s plate 626: a thoroughbred mare galloping. Five frames from this gif encoded into the E. Coli genome. Source: Wikimedia Commons

Every pixel of this movie was represented by a black and white binary colour code. Over five days, this binary code was introduced into an Escherichia coli colony via a synthetic DNA sequence. Each nucleotide (an A, T, C or G) made up two digits of binary, and each day a new frame of the film was presented to the bacteria.

They were then allowed to propagate for three weeks, and broken open for their DNA. Following DNA sequencing, the researchers could put the pieces of the film back together with 90% accuracy. Nevertheless, they could watch a slightly grainy version of the mare gallop through the countryside.

Act 3: To Be Continued…  

This technology may help us understand how cells in hard-to-get places, such as brain neurons, develop into different cell fates over time. Experimental biologists could use this technique to catalogue environmental or internal cues cells experience over time. The researchers hope to continue creating molecular recording methods in other cell types, and engineer the system to record natural events.