Genomes can now be entrusted to store information about a variety of transient biological events inside of living cells, as they happen, like a flight recorder collecting data from an aircraft. "Our method, which goes by the acronym ENGRAM, aims to turn cells into their own historians," said Dr. Jay Shendure, a professor of genome sciences at the University of Washington School of Medicine and scientific director of the Brotman Baty Institute for Precision Medicine. ENGRAM stands for enhancer-driven genomic recording of transcriptional activity in multiplex. The acronym was inspired by a neuroscience term that refers to the physical basis for a memory.

 

ENGRAM couples each kind of biological signal or event to a symbolic barcode. This approach offers a novel method for recording and complements previously developed molecular recording techniques. This new strategy traces and archives the type and timing of biological signals by inserting this information into the genome. For example, this can include keeping tabs on the commands that turn genes on or off. Such recordings might hold clues to what occurs within stem cells to spur them into becoming different cell types. It might also offer insights into other questions about how cells operate, and how their past influences their future. In today's Nature paper, Shendure and his team described how symbolic recording can follow the actions of non-coding DNA regions that control the protein production of neighboring genes. They also demonstrated how ENGRAM and DNA Typewriter can be combined. The scientists were able to record cell-type specific activities of dozens to hundreds of these sorts of gene-regulatory elements.

 

"As we were inspired by new advances in the CRISPR field for developing both the ENGRAM and DNA Typewriter systems, I imagine that these papers will inspire others to further improve genomic recording technologies -- such that maybe one day we will record the entire history of cells," said Junhong Choi. The researchers developing ENGRAM say that work is still needed to realize what it and related genome-based recording technologies can potentially do. "This is a strategy for capturing biological information in living systems. It is not specific to a particular field like cancer or neuroscience and hopefully will be useful across the board," Shendure said.