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Dirk Trauner, other UC researchers win major NIH nanomedicine grant

Dirk Trauner

A research center newly created by the University of California, Berkeley, and Lawrence Berkeley National Laboratory (LBNL) aims to put light-sensitive switches in the body's cells that can be flipped on and off as easily as a remote control operates a TV.

The UC Berkeley-LBNL Nanomedicine Development Center got off the ground this month thanks to a $6 million, five-year grant from the National Institutes of Health (NIH), part of a nanomedicine initiative within NIH's Roadmap for Medical Research.

One major goal of the research is to equip cells of the retina with photoswitches, essentially making blind nerve cells see, restoring light sensitivity in people with degenerative blindness such as macular degeneration.

The nanoscience breakthrough at the core of the research was developed at UC Berkeley and LBNL over the past several years by neuroscientist Richard Kramer, professor of molecular and cell biology, Dirk Trauner, professor of chemistry, and Ehud Y. Isacoff, professor of molecular and cell biology and chair of the Graduate Group in Biophysics at UC Berkeley. All three are members of the Physical Biosciences Division of LBNL.

"The research will focus on one major application: restoring the response to light in the eyes of people who have lost their photoreceptor cells-in particular, the rods and cones in the most sensitive part of the retina," says Isacoff. "We plan to develop the tools to create a new layer of optically active cells for the retina."

Loss of photoreceptors - the light detectors in the retina - is the major cause of blindness in the United States. One in four people over age 65 suffers vision loss as a result of this condition, the most common diagnosis being macular degeneration.

The researchers' development involves altering an ion channel commonly found in nerve cells so that the channel turns the cell on when zapped by green light and turns the cell off when hit by ultraviolet light. The researchers demonstrated in 2004 that they could turn cultured nerve cells on and off with this optical switch. Since then, the researchers have worked with UC Berkeley Professor of Vision Science and Optometry John Flannery to inject photoswitches into the eyes of rats that have a disease that kills their rods and cones. The photoswitches have restored some light sensitivity to the remaining retinal cells.

"Until recently, progress in the neurosciences has been hampered by a lack of structural understanding of the basic components that underlie the function of excitable cells: the receptors and the ion channels," says Trauner. "With the emergence of the first X-ray crystal structures of these proteins, this situation has changed dramatically. Neurobiology is bound to mature into a truly molecular science, and we believe that the time has come for organic chemists to make an impact on this field."

For the new NIH center, Trauner's group will focus on attaching the small-molecule photoswitches to proteins. The new center will also engage the skills of chemical engineer David Schaffer, who will help with the viral vectors that insert the modified proteins into cells.

"Five years from now I think we'll see not only clinical studies emerging from this research," says Trauner, "but also new photochemical probes to study signal transduction and many other facets of neurobiology and biochemistry more broadly."

One emphasis of the NIH Roadmap Initiative is "translational research" that speeds the movement of new discoveries quickly into new drugs and procedures. "Our research is a good example of the translational research the NIH is seeking," says Trauner. "I am amazed how quickly this program has matured from a fundamental study on manipulating nature's molecular machines to an effort to actually cure blindness".

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