19 July 2018 – Observing what goes on in a single cell at a defined location within the body is a problem that has occupied biologists for many years. Immunology, with its need to deal with the fluid, ever-changing nature of the immune system, has been particularly vexed by this issue. So it’s not by chance that two immunologists, Matteo Iannacone from the San Raffaele Scientific Institute in Milan, Italy and Ido Amit from the Weizmann Institute of Science in Rehovot, Israel, together with Ziv Shulman, also at the Weizmann Institute, have finally cracked the problem, in a collaboration that’s produced a technical tour-de-force called NICHE-seq.
Their recent paper (doi: 10.1126/science.aao4277) describes using two-photon microscopy to switch on a ubiquitously-expressed photo-activatable fluorescent reporter protein in a specific cell niche, either in a transgenic animal, or ex vivo. Once marked in this way, the cells are purified by flow-sorting, and individually subjected to massively parallel single-cell RNA sequencing, giving a genome-wide transcriptional readout that can be linked to a precise location. This breakthrough has opened up a whole new vista of research and biomedical possibilities, and the collaboration is now expanding to include both the academic and commercial sectors.
Chance encounter
Amit and Iannacone first met as postdocs over ten years ago, when they were on the same plane to a meeting in Japan. They kept in touch sporadically, but it wasn’t until they both became EMBO Young Investigators that they started to bump into each other on a regular basis. In the intervening years, Amit had become an expert in immunogenomics, and Iannacone in intravital imaging, and they quickly realized that combining their knowledge might be synergistic. “We both shared a common passion and interest in this problem, but separately, we didn’t have the technological understanding to actually solve it,” says Amit.
“We were both pushing the limits of the technology, one related to looking in real time at immune cells within living organisms, and the other in doing large scale single cell RNA sequencing analysis on organs,” Iannacone says. “While discussing this we came up with the idea to get together and see if Amit’s lab could read genome-wide expression patterns in cells that my lab could label and purify. That’s what triggered the collaboration.”
Crucial time for meeting people
Both researchers are enthusiastic supporters of the EMBO Young Investigator Programme: “You need a spark to start a big fire and I think that’s what being an EMBO Young Investigator allows you to do,” Amit says. “Having this ability to go to Young Investigator Meetings and think together in a different atmosphere is a very important bridge that allows people to meet and discuss their work. And the resulting cross-pollination between fields has been a major force in the kind of research we both do.”
You need a spark to start a big fire and I think that’s what being an EMBO Young Investigator allows you to do.
Ido Amit, Weizmann Institute of Science in Rehovot, Israel
Iannacone agrees: “EMBO funded some exchange visits between our two labs, which really drove the project forward,” he says, “but the most critical aspect for me is the possibility of networking and meeting people like Ido in the crucial early years of building my group. Being able to collaborate to bring our research to fields we’d never thought of before is incredibly valuable. There’s no other programme quite like it.”
Thinking back to their first mid-air encounter all those years ago, Amit has a final tip: “Maybe the lesson is that when you meet someone, you should be as open and friendly as possible. Talking science with someone you like is not only fun; it can take you to exciting and unexpected places.”
