Scientists Turn Mysterious Cell ‘Vaults’ Into a Diary of Genetic Activity Through Time

In the 1980s, UCLA cellular biologist Leonard Rome noticed odd, barrel-shaped structures present in almost all cells. The hollow particles were filled with RNA and a handful of proteins. Naming them vaults, Rome has tried to understand their purpose ever since.

Though vaults remain enigmatic, their unique structure recently inspired a separate team. Led by Fei Chen at the Broad Institute of MIT and Harvard, the scientists engineered vaults to collect and store messenger RNA (mRNA) molecules for up to a week. The mRNA vaults they created act like ledgers that detail which genes are turned on or off over time.

In several tests, opening the vaults and reading the mRNA stored within shed light on gene activity that helps cancer cells evade treatment. The method, called TimeVault, also tracked the intricate symphony of gene expression that pushes stem cells to mature into different cell types.

The work is “superpowerful” and “very innovative,” Jiahui Wu at the University of Massachusetts, who was not involved in the study, told Science.

Jay Shendure, an expert in cellular recorders at the University of Washington, agrees. It took “some creativity and some guts” to transform vaults into time capsules, he told Nature.

A Cell’s Life

Each cell is a metropolis humming with activity. Proteins zoom across its interior to coordinate behaviors. Structures called organelles churn out new proteins or recycle old ones to keep cells healthy. Scores of signaling molecules relay information from the environment to the nucleus, where our DNA resides. All this information causes the cell to turn certain genes on or off, allowing it to adapt to a changing biological world.

Scientists have long tried to spy on these intricate cellular processes. Using a common tool, they can tag molecules with glow-in-the-dark protein markers and track them under the microscope. This provides real-time data but only for a handful of proteins over a relatively short time.

Another approach takes snapshots of which genes are active in single cells or groups of cells, usually at the beginning and end of an experiment. Here, scientists extract mRNA, a molecule that carries gene expression information, to paint an overall picture of a cell’s current state. Comparing genetic activity between one point of time and another provides insight into the cell’s history. But unlike a video, these snapshots can’t capture nuanced changes over time.

More recently, a slew of cell recorders based on the gene editor CRISPR have galvanized the field. These tools encode information about cellular events into DNA, essentially forming a “video” of events inside cells that can be retrieved later by sequencing the DNA. Genomic recordings are relatively stable and have been used to map cell lineages—a bit like reconstructing a family tree—and record specific cell signals, such as those responding to viral infection, inflammation, nutrients, or other stimuli. But because they directly write into DNA, the process takes time and could trigger off-target effects.

Enter the Vault

Instead of tinkering with the genetic blueprint, mRNA may be a safer choice. These molecules carry protein-making instructions from DNA and have a relatively short lifespan. In other words, they reflect all the active genes in a cell at any moment, making them perfect candidates for a time capsule. But without protection, they’re rapidly destroyed—often within hours.