Scripps Florida Scientists Awarded $3 Million NIH Grant to Accelerate Identification of Learning and Memory Genes
By Eric Sauter
The Scripps Research Institute has been awarded a three-year, $3.2 million grant by the National Institutes of Health (NIH) to identify the full spectrum of genes involved in learning and memory in Drosophila, the common fruit fly. The research could lead to a number of new therapeutic targets for several major cognitive and neurological disorders, including Alzheimer's disease.
Ronald Davis, chair of the Scripps Research Department of Neuroscience on the Florida campus, is the principal investigator for the project.
Past research has shown that genes involved in Drosophila olfactory learning are remarkably similar in both structure and function in mammalian organisms.
"A large number of genes we expect to identify in Drosophila over the next several years should, in fact, play analogous roles in human learning and memory," Davis said. "As a consequence, our discoveries could provide several new candidate genes that could become potential targets for the development of drugs to treat a range of cognitive disorders."
Because Drosophila learning genes underlie specific behavior, they have long been considered test genes for understanding human brain disorders. For example, the Drosophila gene known as dunce helped define the human form of the gene as a serious risk factor for the devastating psychiatric condition of schizophrenia; and the Nf1 gene, which underlies neurofibromatosis type 1, a human genetic disorder, is important for cognition in both humans and flies.
"We're still early in the process of making connections between Drosophila memory and learning genes and the pathology of human disease," Davis said, "but it's already clear that many of these genes will provide potentially important insight into human brain disorders."
Screening the Fruit Fly Genome
A major objective in the field of learning and memory is to identify all gene products that have essential roles in this complex neurobiological process. Employing some recently developed, genome-wide RNAi transgene libraries of Drosophila genes, Davis said they expect to screen more than 90 percent of the genome for genetic functions involved in acquisition, short-term memory stability, long-term memory, and retrieval.
Davis said they would screen approximately 15,000 RNAi transgenes to cover most of the Drosophila genome; at its most basic, a transgene is a DNA sequence that has been implanted into a new organism. Drosophila RNAi transgenes can inactivate gene function, which allows scientists to systemically analyze specific gene function in a range of tissues.
"Our approach will also utilize techniques recently developed in our laboratory to induce transgene expression in neurons of the adult brain," he said. "This approach will allow us to identify the spectrum of genes across the Drosophila genome involved in learning, stabilizing, and retrieving information about odors – the most commonly studied learning process in fruit flies."
RNA interference (RNAi), which consists of microRNA and small interfering RNA, helps control the selection and activity of genes. These small RNAs can increase or decrease the activity of other RNAs by binding to them, helping direct gene expression, and protecting cells against viral mutation.
These properties make RNAi valuable for the kind of advanced large-scale screens developed by Davis and his colleagues. Because RNAi can shut down genes in the cell systematically, it can help identify various components involved in cell processes or a specific event such as cell division.
As the research progresses, Davis said he plans to construct a website to make the results of these new screens more widely available.
Send comments to: mikaono[at]scripps.edu
"A large number of genes we expect to identify in Drosophila over the next several years should, in fact, play analogous roles in human learning and memory," says Ronald Davis, chair of the Department of Neuroscience. (Photo by James McEntee).
