Seeing the Impossible

Scott Fraser applies the tools of engineering, chemistry and physics to research in imaging and molecular analyses of intact biological systems, with an emphasis on early development, organogenesis and medical diagnostics.

Overlapping Interests By Donna Hesterman If you want to understand how a heart develops inside a growing mouse embryo, your best bet is to watch one -- live. That’s how Scott E. Fraser would approach the problem. Fraser is a biophysicist and a recent USC transformative faculty member hire. He and his colleagues are best known for their work developing light and MRI microscopes that allow scientists to observe living cells in their normal environment in vivo rather than isolated cells swimming in petri dishes. He says that his inventions are often an amalgamation of technologies from different fields, and that he prefers to work along what he calls the “hyphenated edge” of physics, where one field of science converges with another. “There is a tremendous amount to be learned where physics, engineering and biology intersect,” he says. “You and a colleague can make important discoveries in your own lab without having to wait for the next supercollider to be built.” Fraser maintains a quick tempo in his own research by developing tools that allow him to make first hand observations – usually by adapting technologies already in use in other fields. When the big question in biology was whether or not stem cells were pluripotent, he borrowed tools and techniques from other disciplines to get a quick answer. He employed a procedure from neurobiology to tag single cells in a living mouse embryo and then used imaging equipment and a low light microscopic camera to follow them as they grew. “Within weeks we had the answer,” he says. “Stem cells are pluripotent -- they can take on many different fates.” Fraser’s imaging innovations mostly focus on “the mesoscale,” a perspective that he says is invaluable for understanding how cells interact with other cells that surround them inside a living organism. “Very often, we don’t need single-molecule resolution, and we don’t need to see through an object the size of an elephant,” he says. The view is considerably broader than what can be observed in a culture dish, but still concentrated on a small enough region within the organism that microscopy is a must. But very few tools and techniques exist for observation at the mesoscale, so it has become Fraser’s niche to develop his own. The kind of imaging technology he creates has the potential to revolutionize medicine, he says. “Medical treatments are best at arresting the progression of a disease, but not so good at reversing the disease and repairing the tissue damage it causes,” he says. “We want to be able to diagnose things like macular degeneration, glaucoma or diabetes before the symptoms become noticeable.” It is this time window, before people report a problem to their doctor that therapies are most beneficial. The goal, he says, is to make imaging technology for detecting disease available for routine screening in the way that blood pressure machines are available at pharmacies or doctors’ offices. Instruments that support pre-symptom diagnostics are particularly well suited for the marketplace, and Fraser has launched several startups over the course of his career. He also holds many patents in chemistry, biology and nanotechnology. “It’s the sort of scholarship of consequence that USC is looking for in transformative faculty,” says Norberto Grzywacz, Chair of the Department of Biomedical Engineering at USC. “Fraser has the experience of discovering things, but more importantly, he knows how to bring it to the public,” he says. “That’s why we recruited him specifically.” The interdisciplinary nature of Fraser’s scholarship has earned him a joint appointment at USC between the Viterbi Department of Biomedical Engineering and the Dana and David Dornsife College of Letters, Arts and Sciences. As a professor at California Institute of Technology, Fraser helped to start up a biological imaging center, a brain imaging center and a nanotechnology center. At USC, he’ll work to establish key facilities, such as imaging centers at the Children’s Hospital Los Angeles, the Keck School of Medicine and University Park Campus. “These places are hotbeds of unsolved problems in medicine and biology,” says Fraser. “Building a center brings together a critical mass of people from different disciplines, and that fosters the sort of cross hybridization that speeds innovation.” The first centers should be up and running by the end of 2012. Fraser says he sees his role as USC’s Director of Science Initiatives to be that of a facilitator, networking between groups to find existing technologies that can be re-purposed for new lines of research. The fruits that can be harvested from the convergence of fields have kept him operating along the hyphenated edges of physics and biology that have served as his inspiration for more than 30 years. “USC has strong programs in molecular biology, computational biology, engineering and medical research,” he says. “If you want to operate at the interface of those disciplines, USC is the place to be.”