Loren Looger, who calls science “an absolute scream,” considers himself lucky to devise tools for neural imaging plus studies of tuberculosis, malaria, diabetes, and cancer.

The long workdays have done nothing to squelch his far-flung curiosity, however. Fortunately, he has found a way to let his scientific pursuits embrace diversity as much as his athletic ones. As his pile of footwear attests, Looger—sporting moss-colored velvet slip-ons—believes in having the right tool for the job, and his lab is dedicated to making that possible. His mission at Janelia Farm, he says, is simple: “do whatever needs to be done.”

Unlike many scientists, Looger doesn’t frame his work around a central question. Instead, by building molecular tools that let his collaborators explore their own questions in new ways, he has constructed a research program that branches into a broad range of biological investigations. At Janelia, where a central goal is learning how circuits in the brain process information, doing what needs to be done means improving researchers’ abilities to visualize neurons, monitor their activity, and manipulate their behavior.

With his knowledge of protein structure and function, Looger can build tools that allow researchers to explore all kinds of biology. He says such tools can be truly transformative for the field of neuroscience, where so much remains unknown. “A little insight can go a long way when applied to questions that are wide open,” he says.

With the success he’s had so far, Looger is coming up with strategies—some rather unconventional—to maximize the impact of his work. He’s not often in the lab, but that doesn’t mean he’s not doing science. He spends most of his day in front of a computer—scouring DNA sequences in search of molecular tricks he can borrow from evolution, using them to alter proteins’ properties in predictable ways, and planning assays to screen for useful tools. He is also likely to be found sifting through articles about research for which his tools might be useful or proposing a new collaboration while he fetches a cup of tea from the campus pub. He calls himself a protein engineer. His Janelia Farm colleague Karel Svoboda calls him a samurai.

What’s calcium got to do with it?

“Loren is the consummate collaborator. He has a very unique skill set, and he is looking for damsels in distress,” Svoboda says. “He’s the kind of person who loves getting involved in other people’s problems, in the very best sense.”

For Svoboda, who investigates the neural circuits that link sensory information to behavior, the most urgent problem is a lack of adequate tools to watch nerve cells signal one another in the brains of active animals. He approached Looger during Janelia Farm’s earliest days, asking the biochemist when they met in 2005 if he could build a protein that signaled the presence of calcium inside cells.

Looger—fresh from a postdoctoral stint in a plant biology lab—couldn’t imagine what calcium had to do with the brain. Svoboda explained that soon after a nerve cell fires, calcium surges inside the cell. By watching the ion’s concentration grow, neuroscientists can monitor neural activity. Protein sensors that emit a fluorescent light to signal the presence of calcium had been used in animals since the late 1990s, but the signals were too weak to reveal much meaningful activity.

By solving the structure of a recent calcium indicator and tweaking its sequence to swap four of the protein’s amino acids for different ones, Looger’s team created an indicator that bound calcium more tightly and fluoresced at least three times as brightly.

The most in demand of any of the tools he has developed, that indicator, GCaMP3, has been distributed to hundreds of labs where it illuminates neural activity that went unnoticed with earlier sensors. Still, neuroscientists are demanding a suite of similar tools that excel at different aspects of calcium sensing, so the overall effort to build better genetically encoded calcium indicators has, like GCaMP3, spread beyond Looger’s lab. Thanks to a large-scale push to generate and evaluate new versions of the protein, GCaMP3 has been mostly superseded by GCaMP5, which produces even less background fluorescence, gives a greater signal in the presence of calcium, and picks up more activity in the brains of living animals. Looger remains integral to that effort, but with a team of Janelia colleagues now sustaining its momentum, he has diverted most of his attention to new projects—lots of them (see Web Extra, “A Kaleidoscope of Projects”).

		A Kaleidoscope of Projects Plenty of mornings, Loren Looger shows up at the Janelia Farm Research Campus not knowing what kind of science he’ll do that day. Read More

Photo: Dustin Aksland

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