work on microscopes
Derek Toomre, assistant professor of cell biology at the 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. Carolyn Slayman, deputy dean of Yale School of Medicine, says, “As
an expert in optical microscopy, Derek works at the interface between biology
and engineering to develop powerful new tools for cell imaging. We are delighted
that his creativity has been recognized by this NIH award.” — By Jacqueline Weaver
T H I S
The five-year grant 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,” says NIH Director Dr. Elias Zerhouni. “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 says.
According to Toomre, 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 insight into how molecules,
vesicles, organelles and whole cells are reorganized in response to internal
and external cues. Toomre says 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 address 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 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. He was appointed an assistant professor at Yale in 2004.
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.The 29 recipients
of the New Innovator Awards were selected out of 2,100 applicants.
“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 says.
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