flamingo_zebrafish_image Vascular system and calcium levels in the larval zebrafish brain, recorded by Michael Weber (Morgridge Institute for Research) using a Flamingo T-SPIM light sheet microscope. Specimen kindly provided by Armin Bahl (Engert Lab, Harvard University; now University of Konstanz).

Beckman Foundation awards Morgridge Investigators to develop smart light sheet technology

Morgridge investigators Jan Huisken and Kevin Eliceiri will lead an initiative to develop and advance light sheet microscopy technology through a grant funded by the Arnold and Mabel Beckman Foundation.

As one of eight awardees, the team at Morgridge will receive $1.2 million this spring to support their proposed project over five years.

Light sheet microscopy has the ability to image samples over several hours or days from different angles to generate a 3D view of an entire organism. This fast-imaging technique generates a tremendous amount of data quickly with less phototoxic effects on the sample.

Jan Huisken
Jan Huisken

“You’re seeing true biology happening in front of your lens,” says Huisken.

Huisken is a founding leader in light sheet microscopy, and he aims to enable more researchers to adopt the cutting-edge technology into their spaces.

“It’s really a new world for some people,” he says. “Suddenly, they’re doing long time lapse experiments. Suddenly they’re looking at three-dimensional tissues instead of single cells on glass slides. So it can be quite transformative for entire labs and entire departments.”

Mary Halloran, professor of integrative biology and neuroscience at the University of Wisconsin – Madison and a collaborating investigator on the grant, sees light sheet microscopy as integral to her research.

“The use of light sheet imaging gives us an unprecedented ability to image neurons developing throughout an entire zebrafish embryo with a remarkable level of resolution and detail,” Halloran says. “This imaging has revealed new information about the molecular mechanisms that regulate the growth of neuronal axons and the formation of neural circuits during embryogenesis.”

While the size and complexity of light sheet microscopy data has prevented wide-spread adoption of the technology, Huisken and Eliceiri plan to use the Beckman Foundation award to make progress toward a “smart microscope” that also can easily be shared with collaborators.

Kevin Eliceiri
Kevin Eliceiri

“The powerful thing about light sheet is the fact that you can empower the biologists to get the view they want,” Eliceiri says.

Eliceiri says that imaging is often like looking at a glass-bottom boat, where a big fish might swim by but then you lose the view. Smart light sheet microscopy, on the other hand, gives you the ability to track that fish where it goes—to follow a biological event rather than having a fixed viewpoint.

“We want to develop something that’s smart and helps us make a conscious decision about what to image, and when to image,” says Huisken. “Then it would process the data in a meaningful way—with the results the biologists are looking for rather than just streaming the raw data onto their hard drives and letting them figure it out after the acquisition.”

Huisken and Eliceiri will co-lead the project with Vikash Singh, professor of biostatistics and computer science at UW – Madison. Singh will play a major role in developing the algorithms and machine learning components of the proposed smart microscope.

Eliceiri adds that he is eager to see their research expand beyond the walls of the institution.

“Jan and I both have this shared view that we want our technology development to benefit others,” he says. “There’s not only the benefit of collaborating directly with us, but we also try to make our tools as relevant as possible outside our groups.”

The portable and modular Flamingo microscope system and the open-source image analysis platform Fiji, which are being developed in Huisken and Eliceiri’s labs, will make it easy to share results.

The team will collaborate closely with several investigators at UW – Madison to benefit experimental progress and foster stronger relationships within the biological imaging community.

“Collaborators on campus and other people at UW are an important partner on this as a testbed to solve their problems,” Eliceiri says. “It’s a good example of Morgridge helping UW and vice versa.”