There’s always a story behind the story. When I talk to researchers about new papers or grants, I ask way more questions than I can possibly cover in the body of a News@Northeastern article. One of my favorite questions to ask is “how did you get interested in this line of work?” It almost always brings with it a great anecdote. Sometimes it’s as simple as “my graduate advisor was working on this stuff and I followed suit,” which is by no means a boring response. I spent nearly a decade working in chemistry labs because my undergraduate advisor inspired me so much. And I’m certain I never would be writing this blog if it hadn’t been for those years. But sometimes the responses are much more unexpected.

One such anecdote surfaced last month when I was talking with Carla Mattos about the a protein called RAS that promotes cellular proliferation. She’s spent thousands of hours thinking about this protein. In fact, she rewrote the book on it: she discovered a novel regulatory mechanism for it when she alighted on something called an allosteric binding site, or a part of the molecule that determines its functional activity at another, remote part. I asked her how she became interested in RAS and she chuckled.

“Oh,” she sighed. “That…That was very, very much by chance!”

Earlier in our discussion I asked her about something I’d read on her website which she casually disregarded as having not much to do with the present study. But it turned out, her work in so-called multiple solvent crystal structures initiated the entire foundation of her current lab.

“Way back as a post doc I was studying protein surfaces using this method,” Mattos told me. She was using organic solvents as probes to detect hot-spots of activity on proteins. They would submerge bulky protein crystals in various organic solvents. Each different solvent environment would create a unique structure, which they would characterize. Then they’d superimpose all the structures atop one another and look for areas of the protein that had lots of different organic solvents converging in the same place. “That correlates very well with affinity hot spots for protein-protein interactions or protein-ligand interactions.”

When Mattos earned her first faculty position back in 1999, the only proteins they’d ever performed this work on were extracellular. “They’re very sturdy, they have disulfide bonds, and I thought back then probably more amenable to be put in organic solvents and surviving.” When she got to North Carolina State, she said, she wanted to look at a new kind of protein with this method. She wanted an intracellular protein that was small and stable enough to survive the method.

She looked around in the literature and landed on RAS. “Of course I didn’t know anything about signalling transduction pathways back then, I barely knew what RAS did.” The first thing she did with the protein was to determine the solvent map. But the data turned up some strange things that she couldn’t explain. Instead of publishing a random new structure without any insights attached to it, Mattos and her team sat on the data and dug deeper into the story of RAS. “In between that data collection and when it finally got published, we went off on this other track of understanding how this protein works and what we were seeing in the data sets.” The publication happened over a decade later and it included an entire paradigm shift for RAS researchers.

Today, Mattos’ work is almost entirely focused on RAS. Her team still does perform solvent mapping, but usually in the context of this particular molecule and its interactions with others.

I love stories of surprise like this. It totally lays bare the intrigue of working as a scientist. It’s all about following your nose, so to speak, asking questions and seeing where they lead you. When one has the freedom to pursue those new leads, amazing things can happen.