In between lab measurements, I found myself dazing off…“Above the polar circle in the vast alleys of Cellsland, the subjects had not yet discovered light and darkness reigned perpetually for months on end. Within this one-of-a-kind kingdom, the inhabitants, a myriad of tiny creatures, relentlessly joined forces to keep their homes up and running throughout the tough months of winter. The kingdom's ruler, Nucleolus, sent coded duties to selected individuals day and night. No one really knew how he assigned a complex network of tasks and to whom or even how they intertwined all together to create a functioning habitat."
“The kingdom thrived, and happiness prevailed until a gloomy turning point. An avalanche engulfed a few key code-readers who suddenly stopped carrying on with their daily tasks. Chaos overtook the kingdom. Not a single creature could pinpoint the source of the problem. Nucleolus wondered if he could only light up the little hard workers in this pitch-dark environment to recognize who performed which tasks, where, and with whom. Nature could brilliantly provide with a flying answer: Fireflies! What if these light-emitting insects could get somehow attracted to and remain bound to the workers for a decent amount of time in order to reveal their actions?” ……..
RNAs are best known as the molecules responsible for translating genetic code into proteins within our cells – a known biological fact. For some time, however, scientists believed that RNAs only existed inside cells. It turns out that they were wrong, and the relatively recent discovery of extracellular RNAs – or simply exRNAs – has shaken the entire scientific community. These exRNAs can travel throughout the body via the bloodstream in tiny little fat bags – a puzzling encapsulated wonder. Today, scientists pursue the quest to understand why cells release RNAs in the first place and what these molecules could tell us when it comes to an individual's health. As you may have guessed by now, RNAs -- extracellular and cellular ones -- are more than ever in the spotlight. When it comes to studying the implications of such molecules within a biological molecular path, this research may bring tremendous value.
Let’s go back to the kingdom of Cellsland. Cellular RNAs are just like its small inhabitants transporting messages from one place to another in a bleak environment. Lighting them up is necessary to follow their interactions with other molecules so scientists can unravel critical biological communications, which, in the long run, could be part of the puzzle in detecting the early onset of a disease, for example. The main goal of my research; however, is to develop this new cellular RNA imaging tool. The techniques used up to date are not as efficient as a researcher would like for two reasons: little contrast, high fluorescent background, and incompatibility with small cellular RNAs (MS2-GFP technique); in addition, they cannot be used in a live functioning cell (FISH technique).
That said, I use a cool microfluidic technology to scan around 10^6 RNA fragments/hour that are able to interact with fluorogenic dyes specifically. These dyes do not emit light in a free state; that is, when not bound to a specific RNA, they would be much like a faded firefly. Yet they light up when bound to an RNA that accepts them, chemically-speaking. The cellular RNA, and therefore its cascade of interactions, can be tracked down over time in a cell, as the RNA-dye complexes can display a fluorescent signal in vitro for around 30 minutes. Is it not, literally, brilliant? (Pause for groans or chuckles). In the future, scientists should be able to light up their molecules of interest more efficiently and for a more extended period with these smaller RNA-dye complexes. Seeing is indeed believing, as one says!
Text by Fernanda Haffner
Illustration by Marion Couturier
This article was written for outreach purposes (Esperluette project).