(Investigator?s Abstract): This application requests funds to purchase a spotter, reader and associated software for establishing a DNA microarray center at UC Davis. The center will provide access for 18 NIH funded investigators to the technology and equipment necessary for generating custom DNA chips. In addition, three centers (Superfund, the NIEHS Center for Agricultural Chemicals and the California Primate Research Center) and students in a number of NIH supported training programs (training grants in Environmental Toxicology, Environmental Pathology, Pulmonary Medicine) will benefit from access to this equipment. As EST sets are established and accessibility of the expertise and equipment needed become greater, we anticipate that there will be more users than listed in the current application. The recent introduction of high throughput techniques for genome wide expression analysis has opened a number of opportunities to understand the variety and complexity of cellular responses to various manipulations. In addition, these approaches have allowed a rapid and more detailed view of alterations in gene expression patterns in response to diseases, which in turn has greatly accelerated the identification of potential drug targets for the treatment of these diseases. While a number of research questions can be answered by the use of DNA arrays, access to the equipment and the cost of commercial arrays has hampered full application of these approaches by many investigators. Much of the work outlined by the major users in this application focuses on changes in target tissues/cells including cells of the pulmonary, reproductive, cardiovascular, neurologic and dermatologic systems in response to a diverse set of agents. In all of these studies the intent is to identify changes, which occur in gene regulation in response to the toxicant, and as a lead toward understanding the critical events leading to toxicity. A second group of investigators will apply these approaches to study of alterations in response to diseases including schizophrenia as well as those associated with susceptibility to viral infections. In all cases the ready availability of flexible technology for generation of sufficient numbers of chips to allow detailed, thorough analysis of changes occurring in transcriptional regulation will both broaden the questions that can be posed by this group of investigators and will increase the speed with which they can be answered.
