SBIR Phase I: Nanobiotechnology for Identification of Membrane Proteins

这个小企业创新研究（SBIR）第一阶段项目将开发一种创新，快速和低成本的纳米技术，非常适合工业规模的膜蛋白结构鉴定。该计划的主要重点是开发一种快速，低成本的方法来制造大的膜蛋白晶体，适用于高分辨率的结构分析。该方法的可行性将建立使用来自三个不同的膜蛋白家族的成员作为结晶过程的原型。电子衍射和微束X射线晶体学使用同步辐射源将用于结构测定。在后续的第二阶段项目中，该技术将进一步优化，以提高分辨率和增加吞吐量，适用于工业规模的应用。该项目的商业应用是在药物设计和开发领域。结构基因组学以高通量的方式识别大量蛋白质结构，已成为结构导向药物设计研究的重要组成部分。膜蛋白是许多疾病的中心介质，包括癌症和病原菌引起的感染。这些蛋白质由于其表达、溶解性和结晶性的问题而对NMR和晶体学提出了挑战。该计划中提出的新方法有望绕过这一瓶颈，并进一步刺激新的发展，以在疾病的最早发展阶段进行检测、诊断和干预。

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.