DNA microarrays provide a sensitive, comprehensive and highly efficient means for monitoring a cell's genetic program. Microarray technology is currently being exploited to determine global RNA expression levels under relevant genetic and environmental conditions. This technical advance, coupled with ever-increasing DNA sequence databases, allows for the rapid identification of functionally related genes, as well as new protein sequence motifs and functional domains. The profound impact that microarray analysis is having on the field of molecular genetics has been the subject of several recent review articles, including an entire supplement in Nature Genetics devoted to this technology. The instrument system proposed in this application, the Genetic Microsystems GMS 417 Arrayer and GMS 418 Array Scanner, will enable investigators at the Wadsworth Center to make use of this valuable technology under affordable conditions. This system was chosen for its quality, state-of-the-art design for producing consistently precise, high-density DNA arrays onto several surfaces, including glass microscope slides, and a confocal laser scanner with high resolution and sensitivity. The Genetic Microsystems Arrayer and Scanner will allow a diverse set of scientists to explore a wide range of biological questions. These include analyzing arrays of mammalian expressed sequence tags (ESTs) to investigate the genetic basis of kidney disease, memory and cerebellar development, identifying human genes important for degeneration and regeneration of olfactory mucosa, determining factors involved in DNA exchange in Mycobacterium, identifying genes controlled by cell cycle regulators in Saccharomyces cerevisiae, analyzing global regulation of transposition and transcription in Escherichia coil, as well as examining nucleic acid binding protein1target site interactions in novel ways. Furthermore, this array system will facilitate the development of improved bioinformatics methods for analysis of genomic expression data.