This Small Business Innovation Research (SBIR) Phase I project will develop an innovative, rapid and low - cost nanotechnology that is ideally suited for industrial-scale identification of membrane protein structure. The main emphasis of this program is to develop a rapid and low-cost approach for fabrication of large membrane protein crystals, suitable for high-resolution structural analysis. The feasibility of the approach will be established using members from three different families of membrane proteins as prototypes for the crystallization process. Electron diffraction and microbeam x-ray crystallography using a synchrotron source will be employed for structure determination. In the follow on Phase II project, the technology will be further optimized to enhance resolution and increase throughput, suitable for industrial-scale applications. The commercial application of this project is in the area of drug design and development. Structural genomics, related to identification of a large number of protein structures in a high throughput mode, has become an integral component of research in structure-guided drug design. Membrane proteins are central mediators for numerous diseases including cancer and infections caused by pathogenic bacteria. These proteins have presented a challenge to NMR and crystallography because of problems with their expression, solubility and crystallization. The new approach proposed in this program is expected to circumvent this bottleneck and to further stimulate new developments, for detecting, diagnosing, and intervening in disease at the earliest stages of development
