Biologists Upload Galloping Horse GIF into the DNA of Living Bacteria
Harvard researchers recently encoded a GIF image into the DNA of a living organism. The research was published on July 12 by Nature.
There is a host of ways to store digital media - USB sticks, SD cards, DVDs - the list could go on for a while. Now DNA has joined the ranks.
DNA computing is fast evolving and soon could hold the entire Star Wars series, all of the favorite tunes, and every cat picture you have ever seen in a tiny device that is invisible to the naked eye. A Harvard University team led by geneticist George Church are realizing the vast storage capabilities of DNA after successfully embedding a series of photos into the DNA of live bacteria.
The five frames researchers selected to encode into the DNA was one of the earliest recordings ever made taken by British photographer Eadweard Muybridge. The series of photos depicts a mare by the name of Annie G. as she gallops in 1887. As one of the first recordings of a biological animal, the chosen images are a commandment and a sort of continuation of Muybridge’s work.
The recent publication of Church and his colleagues' work is a magnificent advancement in molecular recording. The work is an improvement of previous DNA encoding techniques that were disruptive to the host cell.
Previous DNA recordings
For a few years, researchers have been developing expensive and intrusive methods that harvest the DNA of live organisms to store digital data outside of the host cells. Unsurprisingly, the cells are damaged in the process and promptly die after the extraction.
Harvard researchers are changing the way data is recorded on DNA by developing techniques that allow living cells to carry and reproduce data throughout their entire lives. The new technique is enabling scientists to program living cells and tap into the information anytime without disrupting the cell life cycle.
Encoding Live DNA with Digital Data
Back in 2016, a joint team from the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) led by geneticist George Church built the first molecular recorder based on the CRISPR system. The technique enabled the researchers to encode data into the genome of living bacteria - in this case, E. coli.
“As promising as this was, we did not know what would happen when we tried to track about 100 sequences at once, or if it would work at all. This was critical since we are aiming to use this system to record complex biological events as our ultimate goal,” said Seth Shipman, a postdoctoral fellow working with Church and the study’s first author.
Now, one year on, the same researchers have proven the functionality of the CRISPR system. The new approach is enabling researchers to encode complex information sequentially as a motion picture.
How CRISPR Works
The CRISPR system is a powerful tool scientists are using to precisely edit genomes. In nature, the system works by encoding information about invasive viral genomes (essentially instructions viruses inject into DNA sequences to trick cells into replicating other virus bodies). Specific proteins within the body can recognize the intrusive code and can edit it by slicing the infected DNA up, extracting the rogue instructions.
Researchers are using the same technique to find specific strands of DNA and implant them with strands containing programmed data.
The process begins by injecting a protein that acts as a molecular scalpel on DNA. The protein is first attached to an RNA sequence (ribonucleic acid - a nucleic acid with the principal role of carrying instructions to encode and decode specific genomes).
The RNA sequence implanted into the protein matches the DNA sequence researchers aim to edit. By inserting it into the protein, it can recognize and attach itself to a specific spot along a strand of DNA. From there, once attached to the target DNA, a chemical reaction splits the DNA strand. The split DNA is then inserted with a new spacer containing the encoded data.
Previously, the technique was utilized to edit DNA sequences that provide the RNA information to recognize, target, and destroy viral genomes inserted by viruses. In place of the instructions to seek and destroy viral genomes, researchers instead implanted encoded information into DNA strands that could later be retrieved as an image.
Picture depicting the steps of CRISPR creating immunity to viral genomes. The same steps are used to encode information within a DNA strand by splitting the sequence and inserting a spacer filled with data. [Image Source: Harvard University]
In the recent published work, scientists use the CRISPR immune system to encode a series of images into the strands of DNA.
The research team introduced their encoded DNA into E. coli bacteria at an astonishingly slow speed of one frame per day over a five day period. Since the CRISPR system inserts the encoded DNA snippets sequentially, by examining the position of each snippet along the DNA strands, the researchers could determine position of each pixel.
“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. “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,” says Seth Shipman, a postdoctoral fellow who assisted Church with the research.
Each pixel is labeled and encoded into a DNA strand sequentially, allowing researchers to extract and decode the information. [Image Source: Harvard University]
Encoding the Future of Humanity into DNA
It is a complex technology, although it allows researchers to specifically target and precisely insert sets of data inside the DNA of living organisms, without harming cells in the process.
“In this study, we show that two proteins of the CRISPR system, Cas1 and Cas2, that we have engineered into a molecular recording tool, together with new understanding of the sequence requirements for optimal spacers, enables a significantly scaled-up potential for acquiring memories and depositing them in the genome as information that can be provided by researchers from the outside, or that, in the future, could be formed from the cells natural experiences,“ explains Church. He continues,
“Harnessed further, this approach could present a way to cue different types of living cells in their natural tissue environments into recording the formative changes they are undergoing into a synthetically created memory hotspot in their genomes."
The researchers hope the techniques could be used as a means for cells to record vital information about how the organs and other bodily systems are functioning.
“One day, we may be able to follow all the developmental decisions that a differentiating neuron is taking from an 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,” says Shipman.
Perhaps in the future, the methods will help medical professionals detect the early onset of disease and better understand the inner workings of the body. Essentially, it is a way for humans to connect and interact with the human body on a molecular level. Or, perhaps a little more bizarrely, program movies into your own living body.
The research is still in its infancy, although it is a promising area of research that is revolutionizing how doctors interact with the human body.
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