SOUTHEAST COLLABORATORY FOR STRUCTURAL GENOMICS

东南结构基因组学合作实验室

• 批准号: 6230970
• 负责人: BI-CHENG WANG
• 金额: $ 398.03万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6230970
• 关键词: biomedical facility; biotechnology; cooperative study; functional /structural genomics; high throughput technology; protein structure; technology /technique development

DESCRIPTION (Taken from the Application): This proposal aims to develop, integrate, and test all of the constituents for carrying out cost-effective, high-throughput structural genomics research for both prokaryotic and eukaryotic systems. The objectives are two-fold: (1) To develop and test experimental and computational strategies for carrying out a cost-effective, high-throughput structural determination of proteins by X-ray crystallography and NMR methods. (2) To apply these strategies to scan the entire genome of an organism at a rapid pace. The eukaryotic organism, Caenorabditis elegans, and an ancestrally-related prokaryotic microorganism having a small genome, Pyrococcus furiosus, are selected as representative genomes. As human cDNAs from the NCl sponsored genome project become available, they will be included in the study with the ultimate goal being structural characterization of all proteins of the human genome. By selecting both prokaryotic and eukaryotic genomes we should be able to explore the full breadth of obstacles to high-throughput structure determination of gene products from any genome. The Pilot Center has three working groups: Protein Production Group, NMR Group, and X-ray Crystallography Group. Using a robotic approach, the protein production group plans to supply approximately 80 proteins/week (1-5 mg each) for both NMR and X-ray crystallographic studies. While the NMR Group has developed methods that potentially could lead to high-throughput methods, the X-ray crystallography group has developed innovative approaches in three areas of protein crystallography. They are: crystallization of proteins using microgram quantity of sample, increased data collection efficiency 3 to 5 times at a synchrotron site, and a breakthrough in phase determination using sulfur anomalous scattering signal. The new process of crystallization will significantly impact the structural genomics in that essentially all proteins, even those that can be expressed in microgram quantities will be candidates for crystallographic studies. The latter is significant in terms of cost-effectiveness for large-scale structure determination as it could allow one to solve a protein crystal structure routinely without the need of substituting the sulfur by selenium atom, saving both time and cost. This proposal aims to integrate these developments and others to produce a system for cost-effective, high-throughput structure determination on both prokaryotic and eukaryotic systems. Once fully developed, this system will dramatically change our speed of structure determination. It will have broad implications to medical science and biotechnology development in this nation.

描述（摘自申请）：本提案旨在开发， 整合和测试所有的组成部分，以实现成本效益， 原核生物和哺乳动物高通量结构基因组学研究 真核生物系统目标有两个：（1）开发和测试 实验和计算策略， X射线晶体学高通量蛋白质结构测定 和NMR方法。(2)为了应用这些策略来扫描一个人的整个基因组， 有机体快速生长。真核生物秀丽隐杆线虫， 具有小基因组的祖先相关原核微生物， 选择激烈热球菌（Pyrococcus furiosus）作为代表性基因组。作为人类cDNA 从NCI赞助的基因组计划变得可用，他们将被包括在内， 在研究中，最终目标是对所有 人类基因组的蛋白质。通过选择原核和真核 基因组，我们应该能够探索的障碍， 对来自任何基因组的基因产物进行高通量结构测定。的 中试中心有三个工作组：蛋白质生产组、核磁共振组和 X射线晶体学组。使用机器人方法， 该小组计划每周为两种NMR提供约80种蛋白质（每种1-5 mg）， 和X射线晶体学研究。虽然核磁共振小组已经开发出了 这可能会导致高通量的方法，X射线 晶体学小组在三个领域开发了创新方法， 蛋白质晶体学它们是：使用微克的蛋白质结晶 样品量，数据收集效率提高3至5倍， 同步加速器位置，以及用硫确定相的突破 异常散射信号新的结晶过程将 对结构基因组学产生了重大影响，因为基本上所有蛋白质， 即使是那些可以用微克数量表示的物质， 晶体学研究后者在以下方面意义重大： 大规模结构确定的成本效益，因为它可以允许 一个是解决蛋白质晶体结构的常规，而不需要 用硒原子代替硫，既节省时间又节约成本。这 一项提案旨在整合这些发展和其他发展，以产生一个系统 用于在原核生物和非原核生物上进行具有成本效益的高通量结构测定， 和真核系统。一旦全面开发，这个系统将大大 改变我们的结构决定的速度。这将产生广泛的影响， 医学科学和生物技术的发展。