Beckman Center Secures $1-Million Grant for Cutting-Edge Lattice Light Sheet Microscope

By Jan Wesner Childs

April 5, 2019

The Beckman Center for Molecular and Genetic Medicine will soon be home to a pioneering imaging technology that allows researchers to observe and document living cells in as close to real time as possible.

The Lattice Light Sheet Microscope  will be housed at the center’s Cell Sciences Imaging Facility.

“It’s a major acquisition,” CSIF Director, Jon Mulholland said. “It is going to enable some really cutting-edge, impactful research. The great thing about this scope is that the lattice light sheet is actually directed horizontally to the detection light path making it very fast, with high resolution, while also being very gentle on the cells being imaged.”

The LLSM is manufactured by 3i Inc.

Besides providing a clearer, brighter 3D image, the thin layers of light are not as damaging to living cells.

“What this means is that it allows us to expand our observation times, making it 50 to 100 times longer without compromising the speed and without compromising the resolution, all the while maintaining cell viability.” Mulholland said, “It’s going to produce huge amounts of data. We’re talking many terabytes of data.”

The LLSM was made possible through a nearly $1-million grant awarded to faculty member Dr. Joanna Wysocka, the Lorry Lokey Professor in the School of Medicine, professor of developmental biology and of chemical and systems biology, and Howard Hughes Medical Institute investigator, by the Howard Hughes Medical Institute, the same facility where the microscope was developed by Nobel Laureate Eric Betzig. Mulholland said the Beckman Center has also secured funding for a 350+ terabyte fast file storage appliance to handle all the data researchers will generate with the LLSM.

"Being awarded the substantial grant for this state-of-the-art microscope from the Howard Hughes Medical Institute stands as recognition of the groundbreaking work of the scientists at the Stanford Beckman Center, and illustrates how the critical Beckman Foundation funds have served to seed additional funds for our mission,” said Dr. Lucy Shapiro, director of the center. “It also recognizes the expertise and leadership of our staff in the Beckman Center Cell Sciences Imaging Facility. This grant will continue to allow the Stanford Beckman Center to excel as a leading research institution."

Wysocka was awarded the grant for her work on transcriptional dynamics and chromatin organization in live embryonic stem cells. She is especially excited about using the microscope to study subcellular structures and molecules in vivo.

“This technology is really game-changing because it really minimizes photo bleaching and phototoxicity while it still maintains the high speed and resolution,” Wysocka said. “Because we are visualizing individual DNA regulatory regions in the cell, we need something that is really high resolution and we need to have something that is compatible with live imaging over extended periods of time.”

For example, Wysocka said, the process of cell transcription takes place in bursts that in the past were difficult to capture over multiple transcription cycles because of photobleaching and toxicity.

“This process of a burst usually lasts for, depending on the gene, for several minutes, followed by an inactive period of several to tens of minutes,” she said.  “At the same time, many processes associated with transcriptional activation need to be measured at the sub-second timescale. Thus, we want to be observing the transcriptional cycle continuously for over an hour or longer, without sacrificing spatial or temporal resolution.”

Wysocka’s grant application also included the work of several other principal investigators whose research will benefit from the LLSM.

And because the Cell Sciences Imaging Facility will house and maintain the LLSM and provide a staff member specifically trained in running the equipment, other researchers will benefit, too.

“It will be a shared resource for everyone,” Wysocka said. "The participating investigators listed on the application are probably just the tip of the iceberg for people who may benefit from using this technology and I am glad we will have access to it on our campus.”

For more information, press only:
Naomi Love
(650) 723-8423

Joanna Wysocka, Ph.D., Professor of Developmental Biology and of Chemical and Systems Biology

Jon Mulholland, Director, Cell Sciences Imaging Facility