The use of DNA arrays in biology will have a profound influence on our understanding of such basic questions as shape and form, cancer biogenesis, gene circuits, drug development, and evolution. One major use of these arrays is to analyze temporal and spatial variation in messenger RNA levels where control and experimental samples can be observed simultaneously. The recent genome-wide analysis of the yeast life cycle under a variety of environmental conditions, similar studies in E. coli and Caulobacter, the recent analysis of different B-cell lymphomas, and the expression profiling of Falciparum are all stunning examples of how micro array analysis will allow us to study not just a few genes at a time, but the entire genetic complement of an organism. This information is of inestimable value, especially when it is combined with other genetical approaches. It will allow us not to catalogue what is used during a life cycle, but it will also low us to ask questions on a genome-wide basis about differences between closely related species, gene regulation during development and after viral infection, and during the progress of tumorigenesis. To use gene array techniques optimally, especially for arrays involving more than a few hundred genes, three integrated work-stations are required, the arrayed itself, a reader to interpret signals on the array, and a robotic system to prepare and analyze DNA templates on the required large scale. This proposal seeks resources for the third of these items. A robotic work-station capable of reformatting, replicating, purifying, and analyzing upwards of 20,000 different DNA samples is proposed. It will be integrated into a Core Multi-user Array Facility supervised by trained technical staff whose responsibilities will be to manage the equipment and train the end-user. The micro arrayed and reader have been constructed in this facility and are now in use. The proposed robotics will be integrated with the arrayed and reader.
