In a nearby lab, Janelia Farm fellow Kristin Branson has been ramping up camera- and computer-based observations of fly behavior to an industrial scale. Putting her computer science background to work, she transformed what amounts to a surveillance camera system into an automatic behavior detector that she and co-workers have used to spy on 300,000 genetically diverse fruit flies. The scientists teach the computers to associate specific fly behaviors with particular patterns of data, which are then embedded within the image files recorded by the cameras. Rather than having someone perform the time-consuming task of making direct observations of flies, one by one, this automatic machine-based approach sums high-throughput observations on aggression and courtship, among other behaviors. The hope is that the quantitative leap in data gathering and analysis will lead to a qualitative leap in understanding how genes orchestrate nervous systems and related behaviors. (See Web Extra sidebar, “Capturing Behavior.”)

		Capturing Behavior Kristin Branson uses high-throughput ethomics to uncover links between fruit flies' behaviors and their genotypes. Read More

Fly Me Through the Cell

Schnitzer is interested in virtual tours of inaccessible places. His group has been developing techniques for simultaneously imaging hundreds of brain cells in live mice to tease out the neural circuitry in the cerebellar cortex that underlies learning and memory. He and co-workers also have developed a microendoscopy technique that enables them to apply fluorescence microscopy to deep-brain structures that had been inaccessible to conventional microscopy, at least in living and behaving mice. Schnitzer’s team mounts tiny microscopes that weigh a fraction of an ounce onto the heads of mice. Central to these devices are micro-optical needles with a lens that can magnify like a typical microscope’s much larger, curved lens—needles that can penetrate deep into the brain and image living cells and tissue there.

And in a project that complements Branson’s, Schnitzer aims to develop instrumentation for massively parallel brain imaging of up to 100 fruit flies at once—both normal flies and those with genetically induced changes. He aims to learn how neural circuits associated with those genetic variations produce and control specific animal behaviors.

Jensen is pushing computational reconstruction of reality in pursuit of scientific understanding in yet another direction. He and visualization experts in his laboratory have been transforming their electron cryotomography data into mechanism-revealing animations. Says Jensen, “If a picture is worth a thousand words, then an animation is worth a million.”

“We have done movies where we fly into cells and look at things from different points of view,” says Jensen. “We have tried to illustrate mechanisms of how things work inside cells.” He believes animations can be powerful educational tools. “Some people still don’t believe that HIV is the causative agent of AIDS, for instance, so they decline treatments that could help them,” says Jensen. “Our animations of HIV’s molecular transformations will help them understand that we are not making this up.”

As researchers move through the early part of Schnitzer’s third phase of biological imaging, Jensen is already imagining what might be a fourth phase. “The ultimate would be a microscope where you could see down to individual atoms while they were being arranged and rearranged inside a cell in its living state,” Jensen muses. “If you could develop an imaging tool like that, the study of cell biology would be all but over,” Jensen says, noting, however, that it would take a century or more to digest such a comprehensive portrait of life. An outlandish vision for revealing biology’s deepest structures and mechanisms, to be sure, but that is just the sort of thinking it takes to unveil molecular biology in all of its elaborate minutiae.

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