The Next Generation

Since moving to Janelia in May 2010, Keller has been constructing the next generation of the light-sheet microscope. Using the new design and latest technology, he expects this iteration of the microscope to perform 40 times faster than the previous version. This faster speed and many additional capabilities will give scientists even more detailed information about the physical and chemical choreography that occurs during development.

Keller plans to use the revamped instrument to continue his embryology research, with a special focus on neural development in Drosophila. He also hopes to expand the technology’s reach to studying early development in other model organisms, including mice, the gold standard lab model for early investigations into human disorders.

In addition to the lab’s core research projects, Keller will have ample opportunities for collaboration. His work dovetails with that of his new Janelia Farm colleagues, including Hanchuan Peng and Gene Myers as well as Julie Simpson and Jim Truman. It was precisely for this kind of interaction that Keller came to Janelia, where integrated teams with very diverse backgrounds aim to break through existing barriers and solve problems.

Keller is working with Peng, a senior computer scientist at Janelia Farm, and Myers, a Janelia group leader, to implement computational solutions to managing the enormous amount of data the microscope will collect. Peng has created a three-dimensional digital map of the fruit fly brain, and his lab is developing a “smart” image acquisition method that can zero in on specific areas of the brain for analysis.

“These techniques,” Peng says, “may well fit with Philipp’s imaging pipeline—to reduce the data volume and produce quantitative analysis at the moment of [image] acquisition.”

Keller is looking to Janelia group leaders Simpson and Truman for their expertise in fly neuroscience, genetics, and novel labeling strategies. Simpson is investigating how genes, neurons, and neural circuits affect fruit fly behavior. “My optical microscopy expertise is limited to commercial confocals,” she says, “so I am eager to see what Philipp’s microscope can do with our specimens.”

The promise of live embryo imaging is unquestionable. Light-sheet microscopy will allow scientists for the first time to describe in detail the processes of development in complex vertebrates; to map the fates of cells as they become specialized; to track the effects of genetic mutations in a living embryo as it develops; and, of most interest to nonscientists, to witness and come to understand how developmental disorders arise.

“There is so much to be done, such an enormous potential,” Keller says. He’s not the only one to say so. In a review published in the same issue of Nature Methods as Keller’s paper, one imaging expert describes light-sheet microscopy and several other new imaging methods as part of a new frontier.

For the moment, using live imaging to answer developmental biology’s numerous lingering questions remains a sluggish endeavor. Keller says only a few dozen labs around the world have built versions of the microscope. But with a commercial version of the light-sheet microscope in the works, Keller hopes he’ll soon have plenty of company within developmental biology to help fulfill its potential.

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