Aaron DiAntonio, M.D., Ph.D. Assistant Professor of Molecular Biology and Pharmacology Washington University in St. Louis Dr. DiAntonio's research seeks to identify molecular mechanisms of synaptic growth during development. He has developed a Drosophila strain with a mutant highwire gene. The gene serves a vital function across a wide range of phyla since nematode, mouse and human genomes all appear to have a single homolog of highwire. The proposed research will use this mutant model to test the hypothesis that highwire encodes for a ligase that adds ubiquitin to target proteins. Dr. DiAntonio's team believes that this process plays a key role in synapse formation. Initial studies will characterize how highwire functions both in vitro and in vivo and characterize enhancers and suppressors of the gene. Subsequent research will examine other gene products that regulate the growth and function of synapses and will test the relevance of the highwire pathway using a mammalian (mouse) homolog of the gene. Ultimately, elucidating the actions of highwire and its homologs could have implications for understanding the fundamental biological processes involved in learning, memory and cognition. K. Christopher Garcia, Ph.D. Associate Professor, Department of Microbiology & Immunology Stanford University Dr. Garcia is developing a method to determine the three-dimensional molecular structures of membrane proteins, particularly G-protein coupled membrane proteins. Over 1,000 G-protein receptors are known, and they are involved in many essential functions such as vision, the "fight or flight" response, and chemical signaling between cells. He has been able to isolate and purify these membrane receptors. The ultimate aim will be to create protein crystals that can be used to determine the precise structure of the receptors, which will aid in understanding how they work and in developing new treatments that target these receptors. Randy A. Hall, Ph.D. Assistant Professor, Department of Pharmacology, School of Medicine Emory University Dr. Hall's lab studies cell receptors for neurotransmitters and hormones. Many of these drugs have unexpected and unwanted side effects because the receptors they target are not fully understood. By studying how the protein building blocks of these receptors combine in different ways, Dr. Hall hopes to understand how hormones and psychoactive drugs can sometimes activate each other's receptors, which can cause significant side effects. He is currently attempting to determine how many of these cell-surface receptors share the same protein building blocks. Catherine S. Wooley, Ph.D. Associate Professor, Neurobiology and Physiology Northwestern University Dr. Woolley investigates how estrogen influences the aging processes in the brain. She had previously shown that a sex hormone seemingly unrelated to brain function can profoundly affect development and maintenance of synaptic connections involved in memory and brain plasticity. She subsequently found that estrogen targets GABA receptors in the brain and demonstrated how this influences synaptic formation. These findings provided physiologic evidence to support epidemiologic observations that low estrogen and limited education act together as partial risk factors for Alzheimer's disease. Phillip D. Zamore Associate Professor, Department of Biochemistry & Molecular Pharmacology University of Massachusetts Medical School Dr. Zamore's research seeks to uncover the mechanism underlying RNA interference (RNAi), a mechanism used by plants, fungi and animals that effectively turns off gene activity. One area of study will focus on the way that small temporal RNA (stRNA) regulates RNAi. Dr. Zamore co-developed an in vitro RNAi system that allows the RNAi pathway to be studied and was instrumental in the discovery of small interfering RNAs (siRNAs), providing the first evidence that siRNAs regulate the RNAi reaction. Using Drosophila as a model, Dr. Zamore plans to investigate how small regulatory RNAs such as stRNAs control and coordinate gene expression during development. His laboratory is developing affinity purification methods to identify the proteins that mediate the RNAi process. Dr. Zamore hypothesizes that the biochemical mechanisms revealed by his research will also elucidate a role played by stRNAs in embryogenesis, since stRNAs also function as regulators of gene expression during development. 2007 2006 2005 2004 2003 2002 2001 2000 1999