Many diseases are associated with the functional states of membrane proteins and macromolecular structures. Because knowledge of structure, as determined by x-ray crystallography, can yield important insight into function, there is currently a great effort by both academic laboratories and by corporate laboratories engaged in drug discovery to expand their database of membrane protein structures. Protein crystallization is at present a time consuming and-tedious manual procedure. It therefore constitutes the rate limiting step in this endeavor. The long-term goal of this work is to develop a fully functioning robotic Macromolecular Crystallization Workstation which will be ready for production and commercial market introduction both in the United States and world wide. Phase I of this proposal will demonstrate that Cyberlab's automated crystallization workstation adequately meets the requirements of protein crystallographers and that it is a flexible, reliable and efficient platform for the screening of macromolecular crystallization conditions. We will initially address the crystallization of water soluble proteins using the vapor diffusion method with both hanging drops (cover slips) and sitting drops (micro-bridges). The effectiveness of our workstation will then be directly applied to the more difficult task of handling detergent solutions with accuracy and precision.Proposed commercial application:Due to the modular nature of Cyberlab's workstations market entry of the crystallization workstation will leverage our entry into a variety of high throughput biological liquid dispensing niche markets. Cyberlab's Workstation differs significantly from existing products. Cyberlab's fundamental technology is considered by a growing customer base to be the best available on the market for their laboratory automation needs and we expect the crystallization workstation to similarly meet and exceed customer requirements.National Institute fo General Medical Sciences (NIGMS)
