Scientists funded by the National Institutes of Health have succeeded in a study that could have remarkable implications of our understanding and perhaps re-scripting of how the human body behaves. The study, which will appear July 12, 2017, in the journal Nature, show for the first time that DNA in living cells can be used to encode not just genetic knowledge, but any random sequential data into a genome.
Neuroscientist Seth Shipman, Ph.D. , a post-doctoral fellow at Harvard Medical School, Harvard’s Drs. George Church, Jeffrey Macklis and Jeff Nivalapreviously, first demonstrated that they could use CRISPR to store sequences of DNA in bacteria. Clustered regularly interspaced short palindromic repeats (CRISPR) is a genome editing technology that allows permanent modification of genes within organisms. The team then used CRISPR to encode and rebuild frames from a classic 1870s race horse in motion sequence of photos – an early forerunner of moving pictures.
The research is heralded as a important jump ahead in the goal to developing a “molecular recorder” that in the future could make it possible to obtain read-outs, for example, of the transitioning internal states of neurons as they develop. The Harvard team sees many possible futures uses for this technology like recording molecular events such as changes in gene expression over time. The researchers eventually wish to use the technology to further explore the brain.
“We want to use neurons to record a molecular history of the brain through development,” said Seth Shipman. “Such a molecular recorder will allow us to eventually collect data from every cell in the brain at once, without the need to gain access, to observe the cells directly, or disrupt the system to extract genetic material or proteins.”
Transcript of Video Below:
Nearly a century and a half ago, the big news
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about encoding and playing back sequential information – the forerunner of movies – was
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all about those horses.
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Over the years, the technology advance to motion picture film, then to tinier and tinier
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videotapes and flash media.
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And we thought that was gee whiz stuff.
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Well, think again.
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Today’s latest news about encoding and playing back sequential information is again about
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those horses – except these movies were encoded in and played back from DNA in living
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bacterial cells.
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Seth Shipman: To be totally honest, the point is not to
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store videos in bacteria.
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Laugh.
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We use the video because it’s a good example of a complex piece of information that has
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both many parts to it – that is many pixel values and a time component.
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So its organized over time.
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And so it was a good way for us to test whether the CRISPR adaptation system that we’re
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using could actually acquire enough information that we could go in and sequence the bacteria
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after we had encoded it and reconstruct the movie.
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So its kind of a way for us to push the technology forward and understand how we will build and
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analyze data as we are scaling up, hopefully to eventually do biological recording.
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My background is actually in neuroscience.
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And so, I was trying to understand how different cells in the developing brain would become
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very distinct types of neurons.
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So they are start as a cell with the same genetic material.
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But over time, they acquire these very distinct cell states.
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So there are different types of neurons.
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And it’s very difficult, from a technological standpoint, to understand how that happens
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in the developing brain.
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Because its happening for many many many cells at once.
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And all kind of locked away within the brain.
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And so to get access to the biological events is quite difficult.
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So what I imagined was if we had a way or recording biological events and storing them
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in the genome, then I wouldn’t have to – as an experimenter – go in and either be watching
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the cells or be kind of disrupting the brain in order to get information out, which then
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disrupts the entire developmental process.
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The overall idea is to use these kind of molecular recorders to gain access to biological phenomena
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that we just can’t see in real time.
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I was making reference to the development of the brain.
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That’s one place where its something that happens both over time and in a biological
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system that’s very difficult to get access to.
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To actually watch the cell biology occur.
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So if we were able to implement a molecular recorder to catalog biological Events over
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time, that’s the type of a system that really would fundamentally change the type of data
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we would pull out of the system.
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Right now, we’re really piloting the idea of encoding information into the genome as
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a way of storing information in life cells.
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An so, it’s in bacteria.
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We are currently supplying the information.
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And over time we really would want to unlock the technology.
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Be able to put it into any cell type.
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And to hook it up to biology.
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It is now functioning in bacteria.
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So there are other things you could think about, like having living bacteria that are
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actually sensing things in their environment and recording them into their own genome.
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So they could be these biological recording devices, sensing recording devices.
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And so they could be out in the environment or just recording things that are happening
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within the cell – and capturing them, storing them in their genomes.
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At any point, we can go back and recover that information.
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This technology definitely has applications for experimental biology.
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So it can be used as a tool for experimental biologists to gather data from cells.
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In the future, it also potentially has applications in the medical field, where a cell has privileged
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access to certain components of your body.
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And if a cell could be gathering information and recording it into its own genome, then
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that cell could be perhaps living within your body and getting that information over time.
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And a clinician could go in and sequence out the genomic locus that has that information
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and see what’s been going on previously.
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So we’re looking at an image of a human hand, which shows a human hand, because it
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was one of the first images that people put onto the natural world.
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And so since we’re encoding images here in the natural world in a different way, we
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decided to recapitulate one of those images.
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And what you’re seeing is the source image – what we started with.
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We then encoded all of the pixel values into the nucleotides of DNA, distributed them over
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a number of strands of DNA, and then put them into bacteria, where the bacteria acquired
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those sequences and captured them into their own genomes.
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After the cells grew for awhile, we then sequenced their genomes and were able to reconstruct
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the image based on the sequencing of the nucleotides that were inserted.
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So then what you’re looking at is also the reconstructed image from the bacteria after
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they were sequenced.
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Here we are looking at a movie of a horse running.
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This was originally taken by Edweard Muybridge.
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And, again, it was one of the first moving images that was made.
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And so we thought that it was an appropriate thing to encode.
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And what we did here was, again, for each frame, break down the pixel values and encode
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them in the nucleotides of DNA across many different strands – about 100 strands for
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each frame of the image.
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And then in this case, we delivered those strands to living bacteria over time.
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So each frame was delivered on a different day over the course of five days.
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And then we let those cells grow for awhile.
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And then we sequenced their genomes.
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Dnd we were able to reconstruct not only each of the frames, but the order of each of the
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frames.
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Because the molecular recording system that we’re using captures the timing information
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of different molecular events.
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The next step would be to hook it up to actual biology.
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So, right now, we were supplying information in the form of synthesized DNA.
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In the future, we want that information to come from biological events that are happening
Originally a Thai native, now proficient in both Thai and English, Lala has experience in writing and online marketing field as a skilled writer, editor and social media marketer. She has a Bachelor's degree in marketing from the University of Chang Mai and has worked as a content manager for online marketing companies in Thailand and America.
