To bring cells into sharper focus, biologists need a world-class imaging facility, and that's exactly what HHMI plans at Janelia Farm. But building such a facility offers challenges of its own.

For starters, developing new microscopes takes a broad range of expertise. For example, Eric Betzig, a physicist and Janelia Farm group leader, has developed a blueprint for a new type of ultra-high-resolution light microscope (see main story) by drawing on mathematics, theoretical and experimental physics, and engineering. To make his blueprint a reality, he'll work with experimental physicists; computer scientists; and electrical, optical, and mechanical engineers to build prototypes and to develop them into reliable instruments. His long-term goal is "to make instruments that are widely used by biologists."

To develop better electron microscopes, Chen Xu, a physicist in HHMI investigator and Janelia Farm group leader Nikolaus Grigorieff's lab who will manage Janelia Farm's shared electron microscope facility, will collaborate with microscope manufacturers like FEI and JEOL to obtain the best electron beams, the best phase plates, and the most sensitive CCD detectors—and customize them. Grigorieff's team will develop fast new computer programs that choose particles to analyze, align them, and piece together a three-dimensional structure.

Developing new microscopes is only part of the challenge. "You also need a facility for [biologists] to do high-end microscopy with established techniques," says Winfried Denk, a leading microscopist who directs the department of biomedical optics at the Max Planck Institute in Heidelberg, Germany. At Janelia Farm, HHMI plans to create several core facilities, including Xu's shared electron microscope facility, to provide expert technical support to the biologists who use them.

Research institutes like the Max Planck Institute and Janelia Farm are great places to develop new technologies, says Denk. "Developing new technology involves taking risks," he says. Academic scientists, with their eye on tenure and their next grant, can't always do that. Research institutes also foster cross-disciplinary collaboration, which is critical for developing new microscopes. At Janelia Farm, physicists will rub elbows with biologists, chemists will talk with computer scientists, and molecular biologists will mingle with mathematicians, says Gerald Rubin, director of Janelia Farm. "We're going to have all those kinds of people working side by side," he says.

— Dan Ferber