The aim of the study is to one day create bacterial cells that can record and provide medically important information about things occurring in the human body, such as when a disease first occurs and how it spreads. This relates to bacteria having the ability to sense changes to their surroundings.
The process to create the recorder involved a process akin to a type of ‘molecular hacking’. Here bacteria, isolated from the human gut, was able to be programmed to record environmental interactions and to time-stamp each interaction.
The process was undertaken using the CRISPR-Cas gene editing technology, exploiting the immune system of microbial cells. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a family of DNA sequences in bacteria In a natural environment, like the human gut, bacteria can copy snippets of DNA from invading viruses (bacteriophages). This is so that subsequent generations of bacteria are able to recognize and repel invasive viruses. The process of doing so creates a chronological record of the bacterial viruses that is retained in progeny cells.
A technology known as CRISPR/Cas9 can be used to effectively and specifically change genes within organisms. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell’s genome can be cut at a desired location. This enables existing genes to be removed and new ones to be added.
For the process of constructing the biological data recorder, the scientists modified a slice of DNA (a plasmid) to give it the ability to create more copies of itself in the bacterial cell, in response to an external signal. A second, separate recording plasmid was designed to trigger the recorder and track time. When an external signal is detected, the second plasmid is activated, leading to insertion. In a way, the genetically designed CRISPR-Cas system functions as a natural biological memory device.
Up until now other studies have shown that CRISPR can be used to store various data in DNA. In addition, synthetic biologists have used CRISPR to store poems, books, and images in DNA (see the Digital Journal article “DNA as a data storage medium: Progress and challenges.”) However, what is special about the new method is the ability to time-stamp these captured events.
The operation is detailed in the following video:
Commenting on the research, Professor Harris Wang, who led the recent study, said: “Such bacteria, swallowed by a patient, might be able to record the changes they experience through the whole digestive tract, yielding an unprecedented view of previously inaccessible phenomena.”
The research has been published in the journal Science. The research paper is titled “Multiplex recording of cellular events over time on CRISPR biological tape.”
