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Pioneering Neuroscientist Hollis T. Cline Joins The Scripps Research Institute

LA JOLLA, CA, October 23, 2008—The Scripps Research Institute has announced the appointment of innovator and neuroscientist Hollis "Holly" T. Cline, Ph.D., as professor in the institute's Departments of Cell Biology and Chemical Physiology.

"Professor Cline's expertise in the neuroscience of vision will be a significant contribution to our world-class program in the neurosciences," said Scripps Research President Richard A. Lerner, M.D. "Her cutting-edge research on how experience shapes the developing brain, her leadership skills, and her enthusiasm for teaching will be great assets to the institute."

Cline is a graduate of Bryn Mawr College and obtained her Ph.D. from the University of California, Berkeley, working with the late Gunther Stent on the transmission of nerve signals in the leech. She moves to Scripps Research in California from Cold Spring Harbor Laboratory in New York, where she was director of research from 2002 to 2006. Cline won a National Institutes of Health Pioneer Award in 2005, an award for highly creative, high-risk research.

"My group is pleased to be in a beautiful new laboratory," said Cline, "but really it's the outstanding intellectual environment at Scripps Research that is most important to us."

At Cold Spring Harbor Laboratory, Cline's research team developed a system to image the changes in connections between nerve cells, or synapses, in vivo in near real time.  The system uses laser scanning two-photon microscopy, which gives high-resolution, "time-stamped" images. This enables Cline's group to perform studies on live Xenopus tadpoles in which the tadpoles are given a visual stimulus and changes in neuronal connections in response to the stimulus can then be recorded. Using this setup, her team has shown that relatively brief visual experiences increase the excitability and sensitivity of the neurons in the brain responsible for processing visual information.

"What we learn is not necessarily going to tell us just about the visual system, but more generally about circuit development," said Cline. "The rules we learn are applicable to all sensory modalities as well as brain regions in other animals."

In addition to continued research on how experience shapes brain connections, Cline's laboratory will be studying how to map brain circuitry and how faulty connections relate to human disorders. In work funded by her Pioneer Award, Cline will pursue work to draw up a basic wiring blueprint of the tadpole's nervous system. In collaboration with researchers at the Salk Institute, she plans to use modified rabies virus, designed to express fluorescent proteins, to light up the nervous system's wiring. Rabies virus infects the nervous system in a "backwards" manner, traveling from the peripheral nerves to the spinal cord and finally to the brain. 

"One big step forward in neuroscience would be to understand the nervous system's connectivity from an engineering point of view," said Cline. "If you want to understand how an electrical appliance works, you have to figure out the wiring diagram—all the connections and if they have a positive or negative output. We need that diagram in order to move forward with understanding how cognition works."

Within the larger question of how experience affects brain development, Cline also plans to explore what happens when that process goes awry, particularly in developmental disorders such as autism and Fragile X syndrome. While these disorders are extremely complex, one thing is clear: "The brains of these children do not develop normally in response to input or sensory experience," said Cline. "The connections in the brain aren't established in response to stimuli in the way that a normally developing child learns associations."

She intends to design model tadpoles—those with a genetic mutation that prevents the normal formation of connections in response to a visual stimulus. These animals could then be screened for drugs that might reverse the defect and allow proper connections to develop.

"Scripps has a reputation for being very active and aggressive in seeking therapeutic strategies," she said. "Trying to figure out how to use my experimental system to design ways of searching for new therapies is a very open, really exciting area to move into."

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus by 2009.


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