Treating the genome as so much living circuitry, synthetic biologists hope to create designer cells, even “computerized” cells. Such cells could, for example, be used as biosensors to record environmental input, which could be stored for long periods, perhaps as long as the cells keep dividing. Stored information could be read in a variety of ways including DNA sequencing.

To date, cells that have been engineered to record environmental information have been capable of digital memory only. That is, they could record only all-or-nothing memories, such as whether a particular event occurred. Now, however, scientists at MIT report that they have created a living system for storing analog memory. The scientists say that their system can reveal how strong a particular environmental input was or how long it lasted.

The MIT scientists—Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering, and graduate student Fahim Fazadfard—presented their findings November 13 in the journal Science, in an article entitled, “Genomically encoded analog memory with precise in vivo DNA writing in living cell populations.”

“[Our platform generates] single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals,” wrote the authors. “When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs.”

The authors added that their platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies.
“You can store very long-term information,” said Dr. Lu. “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 system presents a couple of different ways to retrieve stored information. If the DNA is inserted into a nonfunctional part of the genome, sequencing the genome will reveal whether the memory is stored in a particular cell. Or, researchers can target the sequences to alter a gene.

For example, in the current study, the new DNA sequence turned on an antibiotic resistance gene, allowing the researchers to determine how many cells had gotten the memory sequence by adding antibiotics to the cells and observing how many survived.

By measuring the proportion of cells in the population that have the new DNA sequence, researchers determined how much exposure there was and how long it lasted. In this paper, the researchers used the system to detect light, a lactose metabolite called IPTG, and an antibiotic derivative called aTc, but it could be tailored to many other molecules or even signals produced by the cell, Dr. Lu explained.
The information can also be erased by stimulating the cells to incorporate a different piece of DNA in the same spot. This process is currently not very efficient, but the researchers are working to improve it.

“This work is very exciting because it integrates many useful capabilities in a single system: long-lasting, analog, distributed genomic storage with a variety of readout options,” commented Shawn Douglas, an assistant professor at the University of California at San Diego who was not involved in the study. “Rather than treating each individual cell as a digital storage device, Farzadfard and Lu treat an entire population of cells as an analog 'hard drive,' greatly increasing the total amount of information that can be stored and retrieved.”

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