Derek Toomre, assistant professor of cell biology at Yale School of Medicine, has received a $2.5 million National Institutes of Health (NIH) Director's New Innovator Award to develop optical techniques for a new generation of microscopes that will help in researching cancer and diabetes, among other diseases.
The five-year grant, announced Tuesday, is among the first group of NIH's New Innovator Awards—which are part of the NIH Roadmap for Medical Research Initiative that tests new approaches to supporting research.
"New investigators are the future of science, and innovative ideas are its lifeblood," said NIH Director Elias Zerhouni, M.D. "The creative scientists we recognize are well-positioned to make significant and potentially transformative discoveries in a variety of areas. The conceptual and technological breakthroughs that are likely to emerge from their highly innovative approaches to major research challenges could speed progress toward important medical advances."
The powerful new microscopes being created in Toomre's lab will permit researchers to watch membrane trafficking and signaling in three dimensions with unprecedented resolution. Toomre's group will apply this technology to understand the trafficking pathways that regulate insulin-stimulated delivery of glucose transporters to the cell surface—a process that is disrupted in type 2 diabetes.
Specifically, Toomre and his colleagues will use the new microscopes to analyze trafficking and signaling at the cell cortex—a region that is a cell's gateway to its environment and is abuzz with activity. It is where molecules are secreted, signaling complexes are assembled, cell-surface receptors are internalized, and the cell's internal scaffolding is remodeled. Studies of the cell cortex are important for understanding secretion, cell migration, and signal transduction and downregulation—and how these processes go awry in diseases such as cancer and diabetes.
"Our ability to understand this important region is limited by our ability to see it in living cells," Toomre said. He said one important challenge facing modern biology is to understand how individual biochemical reactions are integrated in space and time. Increasingly, new vital probes and optical methods have begun to provide unique insight into how molecules, vesicles, organelles and whole cells are reorganized in response to internal and external cues.
Toomre said that "only by pushing new instrumental and quantitative methods in imaging can an important emerging challenge be met—integrating complex information in dynamic cellular systems." Many of the cellular activities that his lab wishes to study cannot be easily seen by traditional microscopy. To tackle this problem, Toomre's lab employs Total Internal Reflection Fluorescent Microscopy (TIRFM), which is based on the same optical principles that are used to transmit information thousands of miles through fiber optic cables. Using an optical sleight of hand, TIRFM can illuminate a very thin section of the lower cortical region of the cell (as thin as 50 nanometers) and thus provide exquisitely high signal-to-background images—so high that even single molecules can be visualized.
A new generation of variable-angle TIRFM microscopes proposed by Toomre's team will prevent artifacts created by conventional microscopes that can obscure the image and will also allow the depth of the light beam's penetration to be rapidly varied. Toomre's innovative and holistic approach spans across instrumentation, cell biology, and quantitative biology.
Toomre graduated from the University of Colorado at Boulder with a B.S. degree and earned his Ph.D. in 1997 at the University of California at San Diego. He did his postdoctoral research in Germany with Kai Simons, an internationally renowned cell biologist. Toomre was appointed an assistant professor at Yale in 2004.
The 29 recipients of the awards were selected out of 2,100 applicants through a special evaluation process that engaged 262 experts from the scientific community in identifying the most highly competitive individuals in each pool. "In addition to supporting outstanding research, these programs represent experiments in new ways of identifying and funding promising but unconventional ideas, especially those from new investigators," Zerhouni said.
The NIH Roadmap for Medical Research is a series of far reaching initiatives designed to transform the nation's medical research capabilities and speed the movement of research discoveries from the bench to the bedside.
Source: YALE University