Click on one of the five organisms to learn about the technology that scientists have invented to study it.

The camera’s automatic digital accounting of the images’ characteristics opened up a world of computer-assisted analyses of what once were only pictures. It also opened options for novel data syntheses, among them visual reconstructions of three-dimensional biological structures from two-dimensional images of consecutive “slices” of a biological sample.

“The third phase of biological imaging is where things have gotten really interesting,” Schnitzer says, adding that the ready availability of powerful computers is as much the driver here as are the microscopes and cameras. Here, he notes, the meaning of the raw data is hard to interpret by eye until a computer processes and reconstructs it into, say, a two- or three-dimensional view with discernible cellular or molecular features. This is akin to the way today’s high-end sonography equipment can reconstruct images of a fetus from sound echoing from it, or the way magnetic resonance imaging machines convert electromagnetic signals from molecules in the body into portraits of internal anatomy. It takes a lot of computing power to turn those raw signals into medically useful pictures.

The Third Phase

Jensen has been pushing this third phase of imaging into the molecular domain. He combines a freeze-prep step—designed to keep water inside cells from evaporating when inside an electron microscope’s vacuum sample chamber—with a multiple-view reconstruction process. The process yields enough 3D clarity, he says, that the resulting images alone can provide sufficient evidence to choose between competing theories about roles played by otherwise mysterious molecular complexes. One example he likes to talk about is the syringe-like mechanism of a molecular defense complex in bacteria whose action had been a matter of speculation. (See Web Extra sidebar, “A CT Scan for Protein Complexes.”)

		A CT Scan for Protein Complexes Grant Jensen's electron cryotomography (ECT) technique lets him view three-dimensional images of macromolecular complexes and small bacterial cells. Read More

At HHMI’s Janelia Farm Research Campus, developmental biologist Philipp Keller has been pushing a different multiview, computer-intensive technique into new biological territory. Called simultaneous multiview light-sheet microscopy, the technique has allowed Keller, a Janelia Farm fellow, to acquire breathtaking movies—they literally evoke gasps—of the daylong embryonic development of fruit flies. He combines computerized tracking of cell lineage, proliferation, and migration with color-coding techniques to make movies of some of biology’s most spectacular performances. (See Web Extra sidebar, “Embryogenesis in Motion.”)

		Embryogenesis in Motion Philipp Keller uses simultaneous multiview light-sheet microscopy to study developing fruit fly embryos. Read More

Meanwhile, Anthony Leonardo, a group leader at Janelia Farm, has been applying a variety of sometimes Hollywood-esque techniques to help answer questions about whole organisms. Here’s one of his questions: How do dragonflies deploy brain-encoded “guidance rules” to execute the acrobatic, high-speed task of capturing prey during flight? In time, he will map the “microstructure of behavior”—among them, details of how the hunting dragonfly orients its head and body—captured in the data from video recordings of the insects’ less-visible neurophysiological and muscular control system. (See Web Extra sidebar, “Eye on the Fly.”)

		Eye on the Fly Janelia Farm group leader Anthony Leonardo employs a pair of high-speed cameras to learn about dragonfly prey capture. Read More

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