SCRIBE Enables Distributed Genomically Encoded Memory

MIT engineers have transformed the genome of the bacterium E. coli into a long-term storage device for memory. SCRIBE (Synthetic Cellular Recorders Integrating Biological Events ) is a scalable platform that uses genomic DNA for analog, rewritable, and flexible memory distributed across living cell populations. They envision that this stable, erasable, and easy-to-retrieve memory will be well suited for applications such as sensors for environmental and medical monitoring.

“You can store very long-term information,” says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering. “You could imagine having this system in a bacterium that lives in your gut, or environmental bacteria. You could put this out for days or months, and then come back later and see what happened at a quantitative level.”The new strategy, described in the Nov. 13, 2014 issue of the journal Science ("Genomically encoded analog memory with precise in vivo DNA writing in living cell populations"), overcomes several limitations of existing methods for storing memory in bacterial genomes, says Lu, the paper’s senior author. Those methods require a large number of genetic regulatory elements, limiting the amount of information that can be stored.The earlier efforts are also limited to digital memory, meaning that they can record only all-or-nothing memories, such as whether a particular event occurred. Lu and graduate student Fahim Farzadfard, the paper’s lead author, set out to create a system for storing analog memory, which can reveal how much exposure there was, or how long it lasted. To achieve that, they designed a “genomic tape recorder” that lets researchers write new information into any bacterial DNA sequence.

The researchers showed that SCRIBE enables the recording of arbitrary transcriptional inputs into DNA storage registers in living cells by translating regulatory signals into ssDNAs. In E. coli, they expressed ssDNAs from engineered retrons that use a reverse transcriptase protein to produce hybrid RNA-ssDNA molecules. These intracellularly expressed ssDNAs are targeted into specific genomic loci where they are recombined and converted into permanent memory. The team could show that genomically stored information can be readily reprogrammed by changing the ssDNA template and controlled via both chemical and light inputs. This demonstrates that genomically encoded memory can be read with a variety of techniques, including reporter genes, functional assays, and high-throughput DNA sequencing.

SCRIBE enables the recording of analog information such as the magnitude and time span of exposure to an input. This convenient feature is facilitated by the intermediate recombination rate of our current system (~10–4 recombination events per generation), which we validated via a mathematical model and computer simulations. For example, the scientists stored the overall exposure time to chemical inducers in the DNA memory of bacterial populations for 12 days (~120 generations), independently of the induction pattern. The frequency of mutants in these populations was linearly related to the total exposure time.

The idea that DNA could be used to store information is an idea that is long familiar to sf readers. Fantasy writer Barbara Hambly uses a similar idea in her 1982 Darwath trilogy. She describes how wizards succeeded in tying information to the DNA of selected individuals.

In the story, several people from 1980's California find themselves transported across the Void to another planet and the Realm of Darwath. They face a deadly species of queerly magical beings - the Dark - who destroyed civilization thousands of years ago. Everything that was made of paper (like books and records) were burned to stave off attacks by the Dark. Tying memories to a few suitable bloodlines was the only way to preserve a record of that period that would endure.

Update 15-Apr-2017: See the Heritable Memories Bloodline from The Time of the Dark (1982) by Barbara Hambly. End update.

Via Scoop.

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