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
  • How to Get Children with Autism to Sleep
    on November 19, 2017 at 12:45 am

    “His pediatric neurologist even said, ‘That is something you can do to make his life calm and easy for him when a lot of things are hard,’” Day says ... particular challenges converge from many biological directions, just like autism itself. […]

  • Gene Frenette: Jaguars’ Lee learned growing up about toughness the hard way
    on November 17, 2017 at 9:32 pm

    He was taken away from the care of his fully deaf biological mother, Toy Williams ... “It’s difficult, but that’s part of my drive for today [as an NFL player],” said Lee. “I don’t really talk too much about family members in my past. […]

  • 'It feels so natural!' 51-year-old mother cries tears of joy as she's reunited with her biological daughter for the first time since giving her up for adoption as a newborn 31 ...
    on November 16, 2017 at 6:52 am

    Knowing she was adopted, she said, was 'hard' because she felt torn between ... and also thinking of her biological daughter. While Angie and Meribeth live only a five-hour drive from each other, they had only communicated by emails and texts before ... […]

  • From floppy disks to flash drives, the history of storage
    on November 16, 2017 at 12:00 am

    Though hard disk drives hold the same magnetic principles of tape ... While there are no literal biological proponents to data storage, the human brain has always been "nature's best brain" and thus continues to be the model for future methods of storage. […]

  • New Model Warns About CRISPR Gene Drives in the Wild
    on November 15, 2017 at 7:00 am

    The perspective also calls for more research on local gene drives — including an untested approach promoted by Esvelt’s lab — that would work somewhat like a standard drive but with biological limits ... it’s hard to tell how well they model ... […]

  • Is cricket a doping-free zone or has anyone been looking hard enough?
    on November 14, 2017 at 4:47 am

    If no one’s being caught, you have to ask how hard anyone’s looking ... The blood testing will allow it to set up a biological passport system, which will allow it to scan for the effects of doping over time, if not detect the substance or method ... […]

  • Biological weapons simulation test planned in Oklahoma
    on November 13, 2017 at 5:26 am

    The Department of Homeland Security announced the small town near the Kansas border will host a biological weapons simulation ... when Monique McNeely was waiting for her food in the drive-through. She says that all she wanted was a coffee and a snack ... […]

  • Teens may be hard-wired to take risks. A new book explains why.
    on November 12, 2017 at 6:49 pm

    Shatkin is willing to walk us through the complicated biological and psychological reasons underlying ... The big takeaway here is that policies that focus on scaring teens, or driving home hard facts about risk, (D.A.R.E., Scared Straight, “Zero ... […]

  • An Adoptive Mother’s Love Flourishes Into Nonprofit Drive
    on November 7, 2017 at 3:00 am

    She says her family of 10 feels just like the right size: four biological children and four children who were ... He went to a kinship family and they decided it was too hard for them, he came back at 3 and a half and then we adopted him,” she said. […]

  • How DNA Could Replace Hard Drives
    on August 17, 2015 at 7:30 am

    Advertisement On hard drives, we use zeros and ones to represent data ... My mind, however, immediately jumped to the biological storage potential. Imagine if you could not only pack your genome into a capsule, but stick your entire biography right ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: