Download Building a better brain--Genomics conference unveils recent findings

Building a better brain--Genomics conference unveils recent
findings
By Leigh MacMillan
June 1, 2001
The human and other genome projects are beginning to bear fruit - in the form of new research
discoveries. Scientists reaping the genome's harvest described recent findings and new
directions last week at the first annual Vanderbilt University Conference on Genomics. The
inaugural conference - "Neurogenomics: Building a Better Brain" - featured research advances at
the crossroads of neuroscience and genomics.
Scientific sessions spanned four days and explored the genes underlying brain development,
neuronal plasticity, drug action, and psychiatric diseases. The value of model systems like fruit
flies, worms, and zebra fish to neuroscience discoveries was also highlighted.
"The ability to move back and forth and up and down the phylogenetic scale is extraordinarily
useful and is a theme that has run through this conference," said Dr. Floyd E. Bloom, chair of
Neuropharmacology at the Scripps Research Institute and honorary chair of the Neurogenomics
Conference.
Bloom praised the conference organizers and the Vanderbilt University scientists who hosted
special topics workshops for the 160 conference participants. "You have seen that this school is
filled with enormous talent and technological expertise," he told participants during closing
remarks.
Speakers in each scientific session described strategies for moving to large-scale genome-wide
screens for genes. Scientists who traditionally have focused on a handful of genes now must
grapple with the 30,000 to 40,000 genes present in the human genome and the even larger
number of resulting protein products.
J. Gregor Sutcliffe, Ph.D., from the Scripps Research Institute, explained a strategy called TOGA
(Total Gene Expression Analysis) that he and colleagues are using to probe how neuropsychiatric
drugs work. Although these drugs occupy receptors immediately, he said, it takes up to three
weeks before they achieve therapeutic effects, suggesting that they work by changing gene
expression. Sutcliffe is using the TOGA method to look for the gene expression changes induced
by these drugs.
Other investigators are using "DNA chips" - nickel-sized pieces of glass spotted with thousands of
different DNA samples - to screen for gene expression changes that accompany processes
ranging from development of the cerebellum to neurodegeneration.
The molecular discoveries made by scientists studying brain development and neuronal
communication come together in efforts to understand neurological disorders and diseases.
"Each complex trait does eventually boil down to specific genes that increase or decrease risk,"
said John C. Crabbe, Ph.D., from the Oregon Health Sciences University.
Speakers in one of the scientific sessions described the search for genes underlying addiction,
autism, and Alzheimer's disease. These disorders represent only a fraction of the known
neurological disorders, but lessons learned in one field will aid efforts in other neuropsychiatric
research fields, said Dr. Eric Nestler, chair of Psychiatry at the University of Texas Southwestern
Medical Center.
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Building a better brain--Genomics conference unveils recent
findings
"We think of distinct diseases and disorders," Nestler said, "but the brain functions in overlapping
circuits, using overlapping signaling mechanisms."
Nestler discussed his group's efforts to characterize the gene expression changes that induce
and maintain a state of addiction. They have identified a gene, delta-FosB, whose expression
increases after chronic drug exposure and after natural compulsive behaviors.
"Delta-FosB could function as a sustained molecular switch that maintains a state of addiction,"
Nestler said, potentially explaining why former addicts relapse after years of abstinence. The
protein might also be a useful target for drugs to treat addiction, he said. Because delta-FosB is a
transcription factor - a protein that turns other genes on or off - Nestler's group now is turning to
DNA chip technologies to identify delta-FosB target genes.
The goal of identifying genes that cause psychiatric disorders or are involved in the
pathophysiology of psychiatric disorders, the scientists agreed, is to develop new diagnostic tests,
new treatments, and hopefully even preventive measures.
At least four different genes have been linked to Alzheimer's disease, and these genes have
"defined a biochemical pathway that we can use to think about treatments," said Peter St.
George-Hyslop, Ph.D., from the University of Toronto. "The endgame is to use our discoveries of
genetic targets and our understanding of the biology to design new treatments."
>As these kinds of strategies are successfully applied to more and more diseases and disorders,
Bloom said, "the world of medicine will have clearly changed."
Vanderbilt faculty members participated in the Neurogenomics conference as scientific session
chairs: Ford F. Ebner, Ph.D., and Randy D. Blakely, Ph.D., presenters: David M. Miller, Ph.D.,
Lila Solnica-Krezel, Ph.D., and Jonathan Haines, Ph.D., and workshop leaders and speakers.
Lee E. Limbird, Ph.D., associate vice chancellor for Research, was the conference convener.
Vanderbilt University will host its second Conference on Genomics, "Proteomics: the Next Grand
Biological Challenge," next May.
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