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EMBL/EMBO Joint Conference 2006

Ulrike Heberlein, University of California at San Francisco, USA

u_heberlein

Ulrike Herberlein

Biography

Ulrike Heberlein performed her undergraduate studies in Biochemistry in her native Chile. After moving to the USA in 1982, she attended graduate school at the University of California at Berkeley, where she worked with Dr. Robert Tjian on the transcriptional regulation of Alcohol dehydrogenase in Drosophila.

After receiving her Ph. D. in 1987, she moved to the laboratory of Dr. Gerry Rubin for postdoctoral training. In the Rubin laboratory, Ulrike worked on several projects related to retinal development in Drosophila. Her most significant contribution to the field was the discovery that the progression of retinal differentiation relied on hedgehog and decapentaplegic, two secreted proteins that have been shown to play crucial roles in many developmental processes in flies and vertebrates.

Ulrike began her independent career in 1993 at the University of California at San Francisco, where she pioneered the use of Drosophila as a model system to study how drugs of abuse, such as ethanol, cocaine and nicotine, affect nervous system function and behavior. These studies have shown that behaviors induced by acute or chronic drug exposure are surprisingly similar in flies and mammals, and that many of the neurotransmitter and second messenger systems that mediate these behaviors are also conserved.

For her innovative work she received the Presidential Early Career Award and the McKnight Investigator Award. More recently, her laboratory has begun studying the role of genes, originally identified in Drosophila, in rodent models of drug addiction. This is the first step in the validation of these genes in a mammalian system, which, if successful, should provide valuable candidate genes for the development of therapies for addiction and for the diagnosis of genetic risk factors.

Ulrike Heberlein is now a Professor in the Department of Anatomy at University of California at San Francisco.

Abstract

Drugs, flies and videotape: What can fruit flies teach us about drug addiction?

Drug addiction is a chronic and relapsing mental illness characterized by compulsive drug use despite serious negative consequences. The cost to society is enormous, yet few treatment strategies exist and those that are available have so far met with very limited success. There is strong evidence from family, twin, and adoption studies, that genetic as well as environmental factors contribute to the risk for drug addiction. It is also well established that multiple genetic loci contribute to this risk and that the constellation of loci involved differs among affected individuals, making identification of specific "addiction genes" a difficult endeavor.

These complexities, together with the high cost of human studies, have led to the development of animal models. Most prominently, rodent models have been used extensively to study how drugs of abuse exert their acute, chronic, and addictive effects. In the last decade, the invertebrate model organisms Drosophila melanogaster and C. elegans – highly accessible to genetic, molecular and behavioral analyses - have been advanced as powerful new animal models to study how abused drugs function in the nervous system to affect behavior. It is becoming increasingly clear that the behaviors induced by acute and chronic drug administration are remarkably similar in invertebrates and mammals, and that at least some of the underlying molecular and neurochemical mechanisms are also conserved.

The use of completely unbiased genetic screens - aided by the ease, quickness, and low expense of invertebrate studies – has led to the identification of novel genes regulating drug-related behaviors. The next phase is to validate these candidate genes, and the signaling pathways and biological processes in which they function, in mammalian model systems and humans. Drug addiction is still not broadly acknowledged as a disease and the associated stigma has hampered the advancement of scientific approaches to treatment. Research on the mechanisms by which abused drugs affect nervous system function and identification of the genetic risk factors should provide novel therapeutic targets and, hopefully, an effective treatment for drug addiction in the near future.