Jul 142017
 

Credit: Wyss Institute at Harvard University
CRISPR system-based technology lets researchers record digital data — such as successive frames of a movie of a galloping horse — in a population of living bacteria. This could eventually have cells record the key changes they undergo during development or exposure to environmental or pathogenic signals.

New CRISPR technology takes cells to the movies

Researchers use expensive machinery to develop ways to harness DNA as a synthetic raw material to store large amounts of digital information outside of living cells.

But what if they could coerce living cells, such as large populations of bacteria, to use their own genomes as a biological hard drive that can record information scientists could tap anytime? That approach 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.

In 2016, a team at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) led by Wyss core faculty member George Church 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 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 they know. In a study published today in Nature, the same team shows in foundational proof-of-principle experiments that developed further as a first-of-its-kind approach, the CRISPR system can encode information in living cells that is as complex as a digitized image of a human hand, reminiscent of early humans’ paintings on cave walls and a sequence of one of the first motion pictures made ever, Eadweard Muybridge’s film of a galloping horse.

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

“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,“ said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School and a Professor of Health Sciences and Technology at Harvard and MIT.

“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,” he said.

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. “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.”

Shipman and postdoctoral fellow Jeff Nivala, the study’s second author, defined a set of requirements they expect will make the spacer sequences easier to acquire, as well as sequence features that prevent their acquisition into growing CRISPR arrays.

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

Learn more: New CRISPR technology takes cells to the movies

 

The Latest on: Biological hard drive
  • “My Kid Won’t Get Out of Bed” Stop the Morning Madness Now
    on July 24, 2017 at 7:43 pm

    Because of the biological drives I mentioned earlier, it may be hard for your adolescent to go to sleep before 11 p.m. Going to bed by 10 is going to be a little “uncomfortable” for your child. In time, the discomfort and annoyance of having to get ... […]

  • Tides on exoplanets could drive alien biological clocks
    on July 24, 2017 at 1:00 am

    Apart from having extremes of temperature, such planets would make it hard for a biological clock to get going. But now it seems that if these worlds also have oceans, then tides could drive a biological clock just like a rising and setting sun would ... […]

  • Bacteria Are the New Hard Drives
    on July 24, 2017 at 12:12 am

    For example, there is still a big difference in storing information in synthetic DNA and in biological DNA. The latter is much more challenging than the former. Living bacteria divide, grow and die in a way that is challenging for the geneticists who are ... […]

  • Treatments on Round Lake target invasive mussels | Local
    on July 23, 2017 at 3:56 am

    “We needed a lake that had both native mussels and invasive mussels present, which was a hard thing to find since the Zebra mussels drive out native ones.” After wanting into the lakes, they might not find a single native mussel in Crooked or Pickerel ... […]

  • Hard-of-hearing Olathe pastor teaches deaf refugees to speak through sign language
    on July 20, 2017 at 12:44 pm

    Two of Buchholz’s biological sons are hard of hearing and the third’s hearing loss is ... “And so, it is a matter of immersing them on having them be around 80 deaf people who drive, and get married and have a family and have a job, so they can ... […]

  • 5 things that can kill your sex drive
    on July 17, 2017 at 11:32 am

    Everyone has different libidos, and different biological sex drives and desires. So if you're not always ... Hitting the bottle too hard is also bad for libido, erectile function, and the quality of your orgasms. […]

  • CRISPR used to build a biological hard drive out of live bacteria
    on July 13, 2017 at 12:17 am

    Hard drives will one day seem as primitive as punch cards or floppy disks, and it may turn out that the medium that replaces them was inside us all along: DNA. There's a mind-boggling amount of data naturally stored in the genome of every organism, with ... […]

  • That really IS a viral video: Scientists store a movie in bacterial DNA in biological hard drive breakthrough
    on July 12, 2017 at 9:28 am

    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 ... […]

  • The Future Of The DNA Hard Drive
    on October 13, 2015 at 7:14 am

    There is little doubt the future of the DNA hard drive is bright. Yet while the biological aspects may be perfectly suited for a variety of applications, the economic and logistic hurdles suggest we should only focus on a few aspirations. For Dr. Narayan ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: