It is the mission of the Protein Structure Initiative to develop an understanding of gene products via structural studies. The size and complexity of genomes precludes the use of standard laboratory techniques if this goal is to be achieved within a single human lifetime. Development of technology and new laboratory protocols are therefore needed. The focus of our R&D is the development and commercialization of """"""""enabling technologies"""""""" using the high-throughput paradigm that has been successfully applied to the Human Genome Project, and to a lesser extent, combinatorial chemistry. A well-known bottleneck in the process of determining macromolecular structures is the generation of crystalline samples. We are seeking funds to design and construct a high throughput crystallization robot capable of handling greater than 10,000 molecular targets per year. Achieving this goal will require the development of new protocols such as handling of very small sample volumes, the creation of new crystallization screens (including the extension of existing 3-component screens), and the development of imaging systems capable of recognizing successful experiments with minimal human intervention. This Phase I proposal seeks funds to conduct feasibility studies to generate engineering drawings, to conduct crystallization studies on an existing robot prototype, and to populate and analyze a crystallization database. In Phase II the high-throughput crystallization robot will be constructed and a crystallization database will be built.
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