SBIR Phase I: Nanobiotechnology for Identification of Membrane Proteins

这个小型企业创新研究(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，非常适合于工业规模的膜蛋白结构识别。该项目的主要重点是开发一种快速、低成本的方法来制备适合于高分辨率结构分析的大分子膜蛋白晶体。将使用来自三个不同膜蛋白家族的成员作为结晶过程的原型来确定该方法的可行性。使用同步加速器的电子衍射和微束X射线结晶学将用于结构测定。在后续二期工程中，该技术将进一步优化，以提高分辨率和增加吞吐量，适合工业规模应用。该项目的商业应用是在药物设计和开发领域。结构基因组学与以高通量方式鉴定大量蛋白质结构有关，已成为结构导向药物设计研究的重要组成部分。膜蛋白是多种疾病的中心媒介，包括癌症和由致病菌引起的感染。由于表达、溶解和结晶方面的问题，这些蛋白质对核磁共振和结晶学提出了挑战。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，用于在疾病发展的最早阶段检测、诊断和干预疾病。

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.