Scientists Collaborate to Create a Lattice Light-Sheet Microscope

To build a high-tech “multi-tool” microscope, St. Jude neurobiologists work with a Nobel laureate and a select team of scientists.

By Keith Crabtree, PhD

Multi-tool microscopy illustration

With a trusty pocketknife, you can open a letter, slice an apple, sharpen a pencil. Yet your options increase—or unfold—if you procure a device that contains multiple tools: scissors, a screwdriver, a magnifying glass and other helpful gadgets.

The next-generation lattice light-sheet microscope, or LLSM, is the high-tech version of a handy tool with more than one function. The term lattice explains the intersection of ultra-thin sheets of laser light; the equipment will also feature adaptive optics, a technology borrowed from astronomers.

Instead of the stars, neuroscientists will be able to see biological systems.

“The new microscope will allow scientists to see for the first time incredibly small features of cells deep within tissues or tumors,” says Michael Dyer, PhD, Developmental Neurobiology chair at St. Jude Children’s Research Hospital.

St. Jude developmental neurobiologists David Solecki, PhD, and Daniel Stabley, PhD, recently acquired a first-generation LLSM for the department’s Neuroimaging Laboratory, a core resource comprising neurobiologists, imaging experts and data scientists. The resolution of this equipment surpasses that of conventional light microscopes. The current LLSM also uses less laser light than other microscopes. Laser light can be toxic to delicate cells.

“The next-generation LLSM will allow scientists to see cellular dynamics with extraordinary clarity,” Solecki says. Dyer, Solecki and Stabley are working with teams at three external labs on the project, the brainchild of Nobel laureate Eric Betzig, PhD, from the University of California, Berkeley.

Like a multi-tool, the next-generation LLSM will smoothly switch from one mode to another, permitting scientists to select different tools derived from decades of technological advancements. St. Jude scientists may one day develop targeted therapies for life-threatening childhood diseases using this technology.

For years, Dyer has studied retinoblastoma, a type of eye cancer that affects young children. When the teams of scientists in this project complete their work, he expects to gain new insight into the biological systems that underpin retinoblastoma—thanks to this handy, high-tech tool.

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