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Caffeine regulates serendipity in the Corridors of ENS

In 2007 I was recruited to the Biology Department of the École Normale Supérieure to launch my own research group; at the same time, Maxime Dahan was moving with part of his team from the Physics to the Biology Department. While the space for my new lab was being renovated, the lab of Olivier Bensaude, right next where Maxime was working, hosted me. As a result, we were often running into each other in the neuralgic center of the floor: the coffee machine. Very fast we started developing joint research projects with the obsession of imaging transcription at the single molecule level.

We recruited Ignacio Izeddin, who was trained as a physicist and specialized in nanophotonics and, in collaboration with Christophe Zimmer at the Pasteur Institute, developed the first PALM microscope in the lab. Ignacio quickly paved the route and solved the hitches and problems that allowed us to detect single protein fluorophores in the nucleoplasm of cells. It was around that time that Ibrahim Cisse joined the group and decided to follow up on our recent observation that the vast majority of RNA polymerase II molecules interacting with an artificial transcribed locus were not engaging in elongation.

Ibrahim was soon performing live cell PALM experiments on the RNA Pol II and something caught our attention. We could not understand why the low-resolution images of the green state of the photoconvertible fluorophore, taken just seconds before the beginning of the high resolution PALM imaging of the red form of the same fluorophore, did not match. Indeed, analyzing the temporal distribution of single molecule detections, Ibrahim discovered that the accumulation of RNA Pol II was transient and highly dynamic, yielding half-lives of only a few seconds. So far the clusters of RNA polymerase had been observed in several cellular systems and they were related to the elongation function. Our finding shows that RNA polymerase clusters are indeed unrelated to elongation and could instead regulate transcription onset.

And this finding started with the collision of a physicist and a biologist in the corridors of the École Normale Supérieure. While this event looked random at the time, I feel now that the weight of several generations of our peers had a lot to do with placing us in those corridors and creating the necessary conditions for the fruitful result of those seemingly random collisions. And coffee, let’s not forget coffee. Just like polymerase clusters are not RNA synthesis factories, coffee brake spots are not sites of active research but rather sites fostering partnerships.