The Allen Institute for Cell Science was officially announced two years ago at an ASCB Annual Meeting by a former ASCB Council member so it seemed fitting for Rick Horwitz, the Institute’s Executive Director, to return to ASCB Council and give its spring meeting an update. “The mission of the institute is to understand and predict cellular behavior in normal, pathological, and regenerative contexts,” Horwitz told Council members gathered last month at the ASCB national office in Bethesda, MD, “And to develop dynamic, visual data on cell organization and activities.”
The Allen Institute was the creation of Microsoft co-founder Paul Allen, who put up $100 million to build a new kind of cell research center, Horwitz said. The new Allen Institute would not compete with researchers in academic labs but would concentrate on providing tools and data that other researchers could build on. He stressed that the institute will “focus on research that cannot be done in a typical academic environment, and will be open and empowering to the community.” One of the first areas where the institute has begun work is on induced pluripotent stem (iPS) cells. “If you look at the cell biology of stem cells, it’s a void,” Horwitz said.
One of the big projects the Allen Institute plans to tackle is a “Google Earth” for the inside of cells, Horwitz said. “We know the linear DNA that exists in cells…but using [DNA] to determine how a cell is organized is like trying to predict a football game by the roster. If one actually watches the play, you learn a lot more,” Horwitz explained. The institute hopes that new methods of high-resolution 3D imaging will determine molecular organization, activities, dynamics, and localization.
Toward that goal, the researchers are using CRISPR/Cas9 to endogenously add a fluorescent tag to proteins so they can be watched in real time. Horwitz showed a number of images of transfected and endogenously tagged proteins in stem cell lines. Not surprisingly, the increased resolution has enabled institute researchers to spot major differences between endogenous and transfected cell lines. “We’ve improved efficiency of endogenous labeling 40-fold; we can produce about 25 [cell lines] a year,” Horwitz said. To help them scale up, they’re working on machine learning to help them differentiate healthy cell colonies from unhealthy cell colonies, he said.
Horwitz said that his researchers hope to provide their edited and vetted cell lines to academic labs for free or low cost. But outside events could intervene, he said. “If you look at the licensing agreement for CRISPR/Cas9 now, there is suddenly a distribution clause that if you distribute then you have to pay. We’re fighting to make it free for everyone.”
Another challenge they’re currently facing is how to do quantitative high-resolution imaging on their edited cell lines. “Lattice light-sheet is hot, but it’s not quantitative yet. It’s not a turnkey instrument. So we’re going with a spinning disk and spectral/airyscan,” Horwitz said. They’re also figuring out ways to integrate information from different experiments, he said.
Horwitz hopes to keep the institute closely involved with ASCB. He’d like to report progress, solicit input, and coordinate and host workshops with the society. Cell biologists need to stick together, Horwitz said, “[Cell biology is] harder than we thought it was when our careers started.”
About the Author:
Christina Szalinski is a science writer with a PhD in Cell Biology from the University of Pittsburgh.
