Scientists store a movie in bacterial DNA

Scientists store a movie in bacterial DNA

It is a truly viral movie unlike any seen before - and could change the future of computing.

Researchers have revealed the first film stored in bacterial DNA, and say it could herald a revolution in digital storage.

The tiny movie, consisting of just five frames, shows a galloping thoroughbred mare named Annie G galloping in 1887, and were taken by the pioneering photographer for his photo series titled Human and Animal Locomotion, one of the first motion pictures ever made.

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The tiny movie, consisting of just five frames, shows a galloping thoroughbred mare named Annie G galloping in 1887. To the left are the original frames. they were encoded into nucleotides and captured sequentially over time by the CRISPR adaptation system in living e. coli bacteria. To the right are the frames after multiple generations of bacterial growth, which researchers recovered by sequencing the bacterial genomes.

HOW THEY DID IT 

The team introduced the DNA into E. coli at a rate of one frame per day for five days.

The researchers then sequenced the CRISPR regions in a population of bacteria to recover the image. 

Because the CRISPR system adds DNA snippets sequentially, the position of each snippet in the array could be used to determine the original frame to which the snippet belonged - allowing the 'movie' to be reconstructed.

 

The team also recorded a human handprint in a nod to the first cave paintings.

In the study published today in Nature, the Harvard team revealed they were able to use the controversial gene editing  CRISPR system to encode information in living cells.  

The team introduced the DNA into E. coli at a rate of one frame per day for five days.

They use nucleotides, the building blocks of DNA, to produce a code that relates to the individual pixels of each image. 

For the GIF, sequences are delivered frame-by-frame over time to living b acteria, where they are inserted into the genome in the order that they were delivered. 

Once inserted into the genome of e.coli, the data can then be retrieved by sequencing the DNA and the images are reconstructed by reading the pixel nucleotide code, which was achieved with around 90% accuracy.

Because the CRISPR system adds DNA snippets sequentially, the position of each snippet in the array could be used to determine the original frame to which the snippet belonged - allowing the 'movie' to be reconstructed.

In practical terms, the breakthrough could not only could open entirely new possibilities of data storage, it could also be engineered into an effective memory device able to create a chronological record of cells' molecular experiences during development or under exposure to stresses or pathogens.

The team also recorded a human handprint in a nod to the first cave paintings. To the left is an image of a human hand, which was encoded into nucleotides and captured by the CRISPR-Cas adaptation system in living bacteria. To the right is the image after multiple generations of bacterial growth, recovered by sequencing bacterial genomes.

The movie that the researchers selected consisted of five frames adapted from British photographer Eadweard Muybridge's Human and Animal Locomotion series.

'The horse was one of the first examples of a moving image and very recognizable,' Seth Shipman, a postdoctoral fellow working with Church and the study's first author told the LA Times. 

'We liked that about it, but we didn't spend a ton of time thinking about it. 

'We weren't sure how the research would go.'

The film build on a 2016 project a team at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) led by Wyss core faculty member George Church which built the first molecular recorder based on the CRISPR system.

The recorder allows cells to acquire bits of chronologically provided, DNA-encoded information that generate a memory in a bacterium's genome. 

The information is stored as an array of sequences in the CRISPR locus and can be recalled and used to reconstruct a timeline of events.

'As promising as this was, we did not know what woul d happen when we tried to track about 100 sequences at once, or if it would work at all,' said Shipman. 

'This was critical since we are aiming to use this system to record complex biological events as our ultimate goal,' . 

The movie that the researchers selected consisted of five frames adapted from British photographer Eadweard Muybridge's Human and Animal Locomotion series.

The CRISPR system helps bacteria develop immunity against the constant onslaught of viruses in their environments. 

As a memory of survived infections, it captures viral DNA molecules and generates short 'spacer' sequences from them, which it then adds as new elements upstream of previous elements in a growing array located in the bacterial genomes' CRISPR locus. 

The CRISPR-Cas9 protein uses this memory to destroy the same viruses when they return. 

HOW DOES CRISPR WORK? 

Crispr technology precisely changes small parts of genetic code.

Unlike other gene-silencing tools, the Crispr system targets the genome's source material and permanently turns off genes at the DNA level.

The Crispr-Cas9 technqiue uses tags, which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

The DNA cut â€" known as a double strand break â€" closely mimics the kinds of mutations that occur naturally, for instance after chronic sun exposure.

But unlike UV rays that can result in genetic alterations, the Crispr system causes a mutation at a precise location in the genome.

When cellular machinery repairs the DNA break, it removes a small snip of DNA. In this way, researchers can precisely turn off specific genes in the genome.

But other than Cas9, now famous as a widely used genome-engineering tool, oth er parts of the CRISPR system so far have not been much exploited. 

The team used still and moving images because they represent constrained and clearly defined data sets; the movie also gave the bacteria a chance to acquire information frame by frame.

'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,' Shipman said.  

In future work, the team will focus on establishing molecular recording devices in other cell types and on engineering the system to memorize biological information.

'One day, we may be able to follow all the developmental decisions that a differentiating neuron is taking from a n early stem cell to a highly-specialized type of cell in the brain, leading to a better understanding of how basic biological and developmental processes are choreographed,' said Shipman. 

Ultimately, the approach could lead to better methods for generating cells for regenerative therapy, disease modeling, and drug testing. 

 

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