New Jackson Laboratory researcher seeks to unravel mysteries of brain development
| Date: May 15, 2006 | 
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Bar Harbor, Maine – The newest addition to The Jackson Laboratory’s scientific staff is an explorer of a largely unknown realm: the human brain. Associate Staff Scientist Zhong-wei Zhang is quite candid that little is known about how our brains develop and operate, and eager to answer a few of the countless questions in his field of neurological research.
“Our brains have about 100 billion neurons, and there are about 1,000 times more synapses than neurons, so there are trillions of connections. It’s extremely complex, and we know very little about how the connections develop, specialize and so on. We learn about it bit by bit, a small piece at a time,” says Zhang, who comes to the Laboratory after six years as assistant professor at Laval University in Québec, Canada.
Zhang’s research interests focus on two pieces of the puzzle that he hopes will yield important insights into the mechanisms of brain development and the consequences if things go wrong. First, he is investigating the role of 5-HT, commonly known as serotonin, in early post-natal brain development. He has found that serotonin produces a very strong excitatory effect in brain neurons soon after birth, but it’s a narrow time window, after which the effect disappears. He hypothesizes that serotonin plays an important role in the maturation of neurons and synapses in the days and weeks after birth.
“What we are doing is disrupting the signaling pathways for serotonin in the brain,” Zhang says. “We work with genetically modified mice, some that already exist and some that we are looking to develop, that have defects at various steps along the serotonin pathways. Then we can assess what happens with these disruptions, including effects on later brain function and overall behavior.”
Serotonin is synthesized from an essential amino acid, tryptophan, that must be ingested through diet, so environmental as well as genetic and physiological factors have a potentially significant impact on serotonin-dependent development. Zhang believes that knowing more about the serotonin pathways will yield better understanding of a variety of developmental disorders—such as autism and Rett Syndrome—and possible clues for interventions.
Zhang’s other research interest involves development in reverse—that is, the “pruning” or elimination of synapses previously formed. This regression lasts until young adulthood and is essential for the development of behavior, but the regulation of pruning in the brain is not understood. Using a multi-disciplinary approach that combines genetics, molecular biology, and electrophysiology, Zhang will investigate the pruning process and its regulation. Again, shedding light on this mechanism offers the opportunity to gain insight not only into essential function, but also disorders that arise from defects in the pruning mechanisms.
It’s challenging work, but Zhang has found outstanding resources at The Jackson Laboratory and is ready to carry his research forward.
“The mice are clearly a great resource, but the Laboratory offers much more. It’s the scientific environment here, the opportunity to collaborate with people who are in related fields but have a slightly different perspective, that make it enriching and exciting. The Laboratory has a strong commitment to multi-disciplinary research, and that’s very appealing to me.”
Zhang is a 1985 graduate of Peking University in Beijing, China. He moved to France for his graduate studies, receiving his Ph.D. in Neurophysiology from Université Louis Pasteur in Strasbourg, France, in 1991. He performed research as a postdoctoral fellow at the University of California, San Diego, from 1991 until 1995 before moving to Laval, where he worked as a post-doc, research scientist, then assistant professor.
Jackson has a strong history of research into the genetics of neurology and neurological disorders. Current investigators who focus principally in neuroscience include Howard Hughes Medical Institute researcher Dr. Susan Ackerman, who works with the genes controlling neurodevelopment and neuron survival. Dr. Robert Burgess also works with neurodevelopment and investigates Alzheimer’s disease. Dr. Wayne Frankel seeks to unravel the molecular mechanisms of neurological disease, with an emphasis on inherited epilepsy. Dr. Verity Letts studies the genetic bases for absence epilepsy. And Howard Hughes Medical Institute researcher Dr. Simon John studies pressure-induced neurodegeneration through his investigations into the genetics of glaucoma.
The Jackson Laboratory, founded in 1929, is the world's largest mammalian genetics research institution, with facilities in Bar Harbor, Maine, and West Sacramento, Calif. Its research staff of more than 450 investigates the genetic basis of cancers, heart disease, osteoporosis, Alzheimer’s disease, glaucoma, diabetes, and many other human diseases and disorders. The Laboratory is also the world's source for nearly 3,000 strains of genetically defined mice, home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.
Contact(s): Mark Wanner, 207-288-6051, mark.wanner@jax.org
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