 |
 |
 |
 |
 |
 |
 |
 |
Karen Berger, Senior Research Scientist Ethanol tolerance, defined as a reduction in the intensity of ethanol’s effects upon repeated exposure, is a hallmark of alcoholism. The molecular changes underlying ethanol tolerance are not well understood. I am utilizing Drosophila as a model organism to study tolerance development. I find that flies, similar to mammals, develop multiple forms of tolerance which can be mechanistically distinguished as well as genetically dissociated. Currently, I am investigating the role of specific genes and pathways in one or more forms of tolerance. Additionally, a collection of fly learning and memory mutants (Dubnau et al., Curr Biol 2003) is being tested for ethanol-related behaviors. This project should allow us to identify components shared between learning and addiction. |
 |
Julie Gesch, Staff Research Associate B.S. - Massechusetts Institute of Technology Hometown: Puyallup, WA |
 |
David Kapfhamer, Post-doctoral Researcher Similar to Drosophila, rodents exhibit many of the simple behavioral responses to acute and chronic ethanol exposure, including alterations in locomotion and development of tolerance. In addition, more complex aspects of addiction may be modeled in mammals, such as voluntary consumption and preference for a particular drug, drug reward and withdrawal. In an effort to extend the results of the lab’s genetic screens in the fly, we are analyzing mice bearing mutations in orthologous genes for altered behavioral responses to drugs of abuse. Often, a single gene in Drosophila is represented by multiple homologs in the mouse. We select murine candidate genes for further study based on several criteria: degree of sequence homology to the fly gene, expression in mesocorticolimbic systems (brain areas implicated in mediating the behavioral effects of drugs of abuse), information gleaned from the scientific literature, and availability of preexisting knockout or gene-trap lines targeting a gene of interest. Despite potential confounds of cross-species functional divergence and redundancy between similar genes in the mouse, we’ve been highly successful in identifying candidate genes that confer altered drug-related phenotypes when disrupted in the mouse and hope these models will provide insight into the neurobiology of addiction. |
 |
Eric Kong, Staff Research Associate I make sure the flies have a good time. Also, I crunch numbers. |
 |
Amy Lasek, Senior Research Scientist Extensive genetic screens in Drosophila have been performed by members of the Heberlein lab to identify genes that mediate acute responses to drugs such as ethanol, cocaine, and nicotine. Many of these genes have never been implicated in drug abuse in humans, but may allow us to elucidate new molecules and pathways that contribute to drug abuse. To further understand the potential role of these genes in behavioral responses to alcohol and other widely abused drugs, we have begun to study homologous genes in rodents. Mice and rats exhibit complicated behavioral responses to drugs, such as reward, withdrawal, sensitization, and tolerance, which may model human drug addiction. I am specifically focused on using RNA interference, a recently described method for reducing the mRNA levels of any gene, as a tool in rodent brain to determine whether previously uncharacterized genes might be involved in responses to addictive drugs. My current work is focused in the Lim-domain only (LMO) genes based on previous work in the Heberlein lab (Tsai, L. et al, PLoS Biol.2:e408, 2004) demonstrating a role for dLMO in motor activation in response to cocaine. |
Fred Wolf, Associate Investigator |