Recording the secret lives of cells
The human body contains trillions of cells, some of which can turn cancerous over time. What makes them go haywire? The cells aren’t talking, which has left scientists to make their best guesses. Now researchers at MIT are fast developing a more surefire way to know – a tiny recorder inserted into a cell that logs its interactions with the surrounding environment.
“Most of the studies we do to understand diseases like cancer and Alzheimer’s involve studying cells in a dish. We’re interested in understanding how cells function in their natural environments,” says Timothy Lu, a biological engineer at MIT and senior author of the paper describing the technique, which ran online in Science on Aug. 18. He collaborated on the technique with graduate students Samuel Perli and Cheryl Cui.
DNA provides a repository for recording information, not dissimilar to computer memory. The researchers created their own recording device by taking advantage of this natural capacity for data storage. They inserted into a cell a short strand of DNA equipped with a sensor detecting exposure to environmental conditions like inflammation, presence of sugar, or activation of a gene, plus CRISPR, the revolutionary gene-editing tool that can be used to make molecular cuts in a strand of DNA.
When the sensor detects a particular stimulus, it triggers CRISPR to make a cut in the short strand of recording DNA. The cell takes it from there. As it does whenever DNA is damaged — be it from sun exposure or an error in the ordinary process of cell division – machinery inside the cell rushes to repair the cut. Usually it achieves these repairs successfully; occasionally it introduces an error into the genetic code. These errors become the record of the encounter.
Later, researchers extract and sequence the recording DNA. The number of differences between the original sequence and the extracted sequence is, in effect, a measure of how often the cell encountered a particular stimulus.
For Lu, this research is the latest turn in an effort to annotate the secret lives of cells. Previously he attempted this using enzymes called recombinases that enable DNA to be flipped once, like a switch. This kind of binary output — either the switch is flipped or it isn’t — can tell you whether an environmental exposure took place or not, but not much more than that. The newer recording technique captures much richer information, providing a record of the frequency or magnitude of an environmental exposure.
While the recording technique — which is being pursued by at least two other unaffiliated laboratories as well — is an improvement over other designs, it’s still a work in progress. Among remaining challenges is the matter of recording a wider range of stimuli.
“For low-hanging fruit [like inflammation] I would imagine it’s ready to go,” says Tom Ellis, a bioengineer at Imperial College London. “If you wanted to do something like [study] cancer, you’d have to respond to different cues.”
That day may not be so far off. Next steps in this research would be to introduce the recorder into, say, a rat embryo, so that every cell in the fully developed rodent would contain the device. Eventually, one day your doctor may be able to read your personal cellular diary the same way she reads your blood pressure.