The spherical structures resemble desert roses and consist of tiny gold platelets "dusted" with platinum particles. Credit: Debasis Maity, Biotechnology and Bioengineering Group / ETH Zurich
Researchers can typically only measure a cell’s current status, not what it did a few hours or days ago. This is a problem if the aim is to understand how immune responses arise or why individual cancer cells survive treatment. It is particularly revealing to know which genes in a cell are active, as this gives scientists key insights into how cells and the body work.
Now, researchers have developed a method that can be used to archive RNA molecules in cells. For the first time, this allows them to examine not only the current state of a cell, but also to reconstruct which genes were active in the past.
For the RNA archive inside the cells, the researchers need to capture RNA molecules and protect them against natural breakdown. This is because molecules of this kind are normally not made to last for long.
Among other things, the scientists achieve this using a protein that occurs naturally in stress granules—accumulations of RNA that form in cells under stress, such as during an infection. In such situations, the cell temporarily shuts down parts of its metabolism and saves RNA molecules for later.
The researchers took this stress granule protein and two other proteins and optimized them using biotechnology. By doing so, they created a system that concentrates a cell’s RNA molecules in a film around the cell’s mitochondria, where it shields the molecules from naturally occurring enzymes in the cells that break down RNA. The researchers introduce the blueprints for the three optimized proteins into the cells via plasmids, and the cells then assemble the archiving system inside themselves. Per cell, this allows several thousand RNA molecules to be archived over several days.
The new method could be used to detect rare events in cells, which is particularly useful if researchers only find out which cells are of interest to them in retrospect. In such cases, they can select these cells and then use the RNA archive to investigate which genes were previously active within them.
The researchers have applied for a patent on the new technology and want to develop it further. One potential area is tumor cells that survive a course of chemotherapy. Cells of this kind can subsequently contribute to a cancer’s recurrence. At present, it is difficult to investigate which cells will survive treatment and how they previously developed.
“Which cells will develop into these persister cells is something that is not known in advance and is poorly understood,” said Christopher Reinkemeier, study author and a postdoc at ETH Zurich. “If we can put our system to use in cancer research, we’ll be able to isolate persister cells and look into their past. This will allow us to research how these cells form and develop and could pave the way for decisive advances in cancer research.”
Data from ETH Zurich