A ‘time capsule for cells’ stores the secret experiences of their past

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Ribosomes, pictured here, synthesize proteins by translating messenger RNA (mRNA) into amino acid chains.Credit: Christoph Burgstedt/Science Photo Library Ribosomes, pictured here, synthesize proteins by translating messenger RNA (mRNA) into amino acid chains. Credit: Christoph Burgstedt/Science Photo Library Researchers have engineered a time capsule for cells, capable of collecting and storing mementos of past activity. The cellular storage units, called TimeVaults, could help unlock secrets to cancer-drug resistance and stem-cell biology, and more broadly how past events shape a cell’s future. The findings were published today in Science1. TimeVaults are made from mysterious cell structures called vaults, which have been modified to collect and store the molecular products of gene transcription, known as messenger RNA (mRNA) molecules. “This is a major step towards a longstanding goal in the field: being able to continuously record transcription in human cells,” says Randall Platt, a biological engineer at the Swiss Federal Institute for Technology in Zurich. “I anticipate that TimeVaults will allow us to observe facets of biology previously inaccessible to us.” Cell recorders Cells change constantly. Researchers tend to study their dynamics in two ways. One method is to watch them live under a microscope, where a limited number of types of molecules can be tracked for days with fluorescent tags. Another way is in test tubes at a single time point, usually the end of an experiment, where mRNA molecules can be measured and compared with those in other cells to reconstruct the past. Over the last decade, researchers have developed a bevy of ‘cell recorders’ - many using CRISPR gene editing - to create an indelible genetic ledger of transient events, such as the activity of a particular molecular pathway over time. This ledger can then be read by genome sequencing to identify the edits later point, creating a timeline of cellular events. But these have a downside: researchers have to decide in advance which events they want to monitor, says Fei Chen, who studies single-cell and genome biology at Harvard University in Cambridge, Massachusetts. In search of an unbiased way of recording of a cell’s lifetime, Chen and his colleagues found inspiration on YouTube. A student in his lab came across a profile of Leonard Rome, who goes under the name of Vault Guy. Rome is a cell biologist at the University of California, Los Angeles, and host of an educational YouTube channel about mysterious, barrel-shaped cellular organelles called vaults. In the 1980s, Rome co-discovered vaults, which are present in the thousands in most mammalian cells. Yet their function has remained unknown ever since. To turn vaults into time capsules, Chen’s team reengineered a vault protein in such a way that it recognizes and links...

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