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Office of Neuroscience Research > Did you know? > Making the invisible visible (Outlook Feature, September 2017)

Making the invisible visible (Outlook Feature, September 2017)

Imaging center brings the science of life to light 

From Outlook Magazine...

Twelve feet tall and weighing several tons, the microscope capable of generating the voltage of a stun gun looms over James Fitzpatrick, PhD, as he circles it, deftly opening latches and detaching panels. A door on the side swings open, revealing a tangle of wires and, near the top, a shelf the size of a tape cassette. When the machine is fully built and turned on, a robotic arm will reach down, pick up experimental samples placed on the shelf and insert them into a column deep inside. There, the samples will be bombarded with electrons.

And the invisible will be unveiled.

This instrument that Fitzpatrick has so painstakingly unsealed is a top-of-the-line cryo-electron microscope. It is capable of magnifying the living world’s tiniest structures — bacteria, viruses and biomolecules — a million or more times, bringing the unimaginably small up to a human scale.

“It’s a complicated beastie,” said Fitzpatrick, grinning. He is director of the Washington University Center for Cellular Imaging, known as WUCCI and pronounced Wookiee. He has spent the better part of the spring and summer overseeing the installation and calibration of the $7.2 million microscope, and he will put it through weeks of testing before making it available to the center’s clients later this fall. The machine is the cornerstone of a significant investment in cellular imaging. Advances in the field are transforming biomedical research, and WUCCI is keeping Washington University at the forefront.

Introducing the WUCCI

WUCCI sprawls across 6,000 square feet in the basement of the McKinley Research Building (to be renamed the Debra and George W. Couch III Biomedical Research Building) on the Medical Campus. It houses 15 of the most advanced microscopes, as well as banks of high-powered computers that are needed to analyze the mountains of data they produce.

The scopes can take 3-D images of viruses, make movies of living neurons as they signal one another, visualize the beating hearts of small animals such as worms and fish and map the structure of proteins down to the location of each atom. Since the center’s establishment in 2015, researchers have imaged everything from living zebrafish and butterfly eyes to plastic catheters and rocks.

Today, more than 500 Washington University researchers representing some 220 labs use the center, and Fitzpatrick is hoping to draw more.

Cornerstone of biology

When Anton van Leeuwenhoek looked through the first microscope more than 300 years ago and saw legions of previously unimagined life forms wriggling underneath, he established one of the foundations of modern biology.

“Imaging is one of the cornerstones of biology and biomedical science,” said Azad Bonni, MD, PhD, the Edison Professor and chair of the Department of Neuroscience. “Whatever questions we’re trying to answer, it all comes down to cells, because they are the fundamental unit of living things.”

Modern research microscopes are as far from Leeuwenhoek’s single-mounted lens as smart phones are from Alexander Graham Bell’s invention. They not only take snapshots of cells mounted on slides, they can record movies of a fertilized egg developing into an embryo, or of an immune cell chasing a bacterium. They can focus deep inside bones, tumors and even small animals, allowing scientists to see cells and tissues in their natural environment. They reveal our DNA. Microscopy makes the invisible visible.

WUCCI builds on the strengths of the departments of Neuroscience and of Cell Biology and Physiology, which operated separate imaging facilities for a number of decades. About five years ago, at funding renewal time, department leaders questioned whether to re-establish separate facilities or join together. “It occurred to us that it might be a good idea to create a collaborative center greater than the sum of its parts,” Bonni said.

The neuroscience imaging facility specialized in light microscopy, which allows researchers to attach fluorescent markers to specific molecules or cells, color-coding their images. Such technology suits researchers who often study how cells respond to cues, and circuits of cells and the synapses connecting them.

Cell biologists lean more heavily on electron microscopy, which images objects tens to thousands of times smaller than cells. Electron microscopes reveal precisely how the essential molecular machinery of the cell operates and how molecules involved in disease might be targeted with drugs.

Members of both departments — Paul Taghert, PhD, and Bonni from Neuroscience, and Helen Piwnica-Worms, PhD, Robert Mecham, PhD, David Piston, PhD, and Phyllis Hanson, MD, PhD, of Cell Biology and Physiology — advocated for this core center and engaged in discussions across the medical school. Taghert and Hanson traveled the country, gathering the best ideas from leading imaging facilities. Ultimately, Fitzpatrick was recruited from The Salk Institute in San Diego.

“We sold him on the idea that he could build something big here,” Bonni said.

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