Stanford researchers have developed a way to use DNA as rewritable digital data storage. Keeping data in cells could have widespread applications in future studies, according to the team, which was led by post-doctoral researcher Jerome Bonnet and Drew Endy, an assistant professor of bioengineering.
“It’s a tool to study processes where you need to track history of cells,” Bonnet said.
“Most of the questions in biology are questions about history,” said Ton Subsoontorn, a graduate student who worked on the research team. “You ask, ‘Why does this cell become a cancer cell?’ and ‘Why does this cell stay a normal cell?’”
Just as a computer chip stores data by flipping an electrical bit or magnetic field on or off, the DNA system flips the orientation of a section of DNA to indicate an on-or-off bit.
The team’s research involved establishing precise control over two enzymes — integrase and excisionase — that work in opposition to manipulate proteins within bacterial cells. The team built on previous research that showed how to irreversibly flip a stretch of DNA about 500 base pairs in length.
“We needed to reliably flip the sequence back and forth, over and over, in order to create a fully reusable binary data register,” Bonnet said. “So we needed something different.”
The team had lots of early success flipping the sequence in either direction independently, but struggled to make both systems work within the same cell to create re-writable data. Endy said that the challenge took 750 trials over three years before the team succeeded.
“We now have enzymes which can bind to the sequence, cut it, flip it and paste it in the new orientation,” Bonnet said.
The enzyme system that Bonnet’s team produced was adapted from the behavior of a virus, according to Subsoontorn. Certain viruses attack bacteria by splicing their own DNA into the genome of the bacteria. The research team’s work used enzymes from those viruses for its manipulations.
According to Subsoontorn, the DNA region being flipped is a promoter, meaning it signals for the expression of another genetic region. In one example, Subsoontorn said the team placed a gene that makes the bacteria glow pink and another that make the bacteria glow blue on either side of the promoter. Flipping the promoter then allowed the team to change the bacteria’s color.
Long-term applications for the idea are far more practical than just color change, the team said. For example, if the system is expanded to have more bits, a cell could record data about its own life cycle, which would be crucial for research on aging and cancerous cells.
“[A cell] can detect arsenic, heavy metals and stuff like that,” Bonnet said. “So you can make basically sensors with memory.”
Subsoontorn likened cells to computing systems. He said that inputs such as light, sugars and other factors determine a cell’s behavior in predictable ways.
“You can think of a cell as an information processing unit,” Subsoontorn said. “You take some input, and it does some kind of logical computation, and it spits out some output.”
He said that keeping data could help bioengineers in particular because they could use the data to learn the behaviors of cells in a system.
The DNA system also represents an advance because silicon computer chips are not yet small enough to fit within cells to take data. However, Bonnet said the DNA system still has advantages in the long term.
“This idea is not trying to compete with silicon memory,” Subsoontorn said. “This is data storage that can operate inside a living cell.”
He said that some cells grow and divide so rapidly that silicon chips would not function, anyway. DNA, however, can grow and multiply along with its cell.
The team said it next hopes to expand the capability of the data storage to a multi-bit system, progressing toward a scale where it can store practical amounts of data for real use.