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Looger’s lab group maintains a tank of the luminescent sea creature known as the brittle star, which dazzles predators by fluorescing when attacked. The researchers are looking for ways to use the long-lasting fluorescence to study neural activity.
All that effort, Looger emphasizes, is ultimately about getting working tools into people’s hands. New tools are thoroughly tested, not just in living cells but in living organisms, and adjusted as necessary to make them more practical. “Loren is not out to prove anything, he just wants to get the right tool to the right person so they can learn something new about biology,” says Luke Lavis, a chemist with whom Looger recently designed a system to target chemicals to specific cells by masking them with chemical shields that can be removed only by a corresponding enzyme. The two tool builders share a friendly rivalry as to whose technique will yield the best results, but ultimately they are working toward common goals. That’s what being a tool builder is all about, Looger says. “If I find a tool in the gutter and it works...we’re done here.”
Hyper to collaborate
Despite his accumulating successes, Looger acknowledges there’s little glory in designing and optimizing reagents for other people’s experiments. “Being a toolmaker can be a bit thankless,” he says. No matter how much it advances science, “the BBC is never going to call you up to talk about the calcium sensor that you made a few percent better.”
He didn’t come to Janelia Farm seeking fame, but it’s an issue he thinks about a lot. To maximize the impact of his work, Looger knows he has to overcome a problem that stymies many toolmakers. Sensors that bind more tightly or shine more brightly than their predecessors tend to be reported in chemistry and engineering journals, which are not widely read by biologists. Subsequent publications, in which the sensors reveal something new about biology, might catch potential collaborators’ attention—but at that point, the toolmaker’s contributions have often been relegated to the fine print.
He has a solution—or at least a strategy. “We are going to hyper-collaborate,” he declares. “We’ll send tools to 1,000 people, and even if just 200 of those acknowledge us, we’ll be hooked into new fields. I have faith that it’s going to work out.”
Looger takes a moment to check in with research technician Gaby Paez. Among other projects, Paez works on improving the stability of a photoconvertible fluorescent protein designed in the Looger lab that changes from green to red when hit by ultraviolet light.
Discovering ways he can contribute to projects he doesn’t yet know he should care about—that’s what energizes Looger most. Though his tools are born out of needs within the neuroscience community, those needs are often mirrored in other fields; in the brain, calcium is a sign of neural activity, but in red blood cells it can signal the presence of a malaria parasite, for example. And Looger’s intuition and “bag of tricks” can be even more broadly applied. A conversation with him can careen from fluorescing starfish arms to the genetics of sex determination in no time, and when he talks about how fortunate he feels to be a protein engineer at Janelia Farm, he ticks off the fields he’s involved with as evidence of his unbelievable luck: “We’re not just working on neural imaging,” he says. “Our tools are being used to study tuberculosis, malaria, diabetes, and cancer, to name a few. I’ve also been dabbling in lupus on the side.”
Committed to his model of hyper-collaboration, Looger says he has 120 projects catalogued on his computer. A few are “someday” ambitions, but most merit Looger’s active attention at least some of the time. A handwritten list of in-progress manuscripts runs two columns in Looger’s notebook and helps keep things on track: circles and stars and sweeps of color compete for urgency, while a handful of completed items are emphatically stricken from the list.
Colleagues at Janelia Farm and elsewhere seek Looger out for his protein-modeling expertise, but he doesn’t wait for people to come to him. “I definitely spam a lot of people,” he laughs, meaning he never hesitates to stop by a colleague’s lab or dash off an email to a stranger saying, in essence, “What if you had a reagent that did this? Would that be useful?” Usually the answer is yes. Sometimes, the answer is “yes, but that’s not possible,” but Looger doesn’t seem to hear the last part.
That willingness to dive in and find out what works strikes colleagues as part of Looger’s inherent optimism, but he says it comes largely from his outsider perspective. Because he’s not entrenched in the dogma of his collaborators’ disciplines, he says, the assumed limits of those fields rarely restrict his imagination. “I don’t know what’s impossible,” he declares. “So we try a lot of things that people say will never work . . . and a lot of it has been successful.”
Photos: Dustin Aksland