SOUTHEAST COLLABORATORY FOR STRUCTURAL GENOMICS

东南结构基因组学合作实验室

• 批准号: 6899658
• 负责人: BI-CHENG WANG
• 金额: $ 5.95万
• 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/6899658
• 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（取自应用程序）：该建议旨在发展， 整合并测试所有成分以执行具有成本效益的成分 用于原核生物和原核生物的高通量结构基因组学研究 真核系统。目标是两个方面：（1）开发和测试 实验和计算策略，用于执行具有成本效益的， X射线晶体学对蛋白质的高通量结构测定 和NMR方法。 （2）应用这些策略来扫描整个基因组 有机体的速度很快。真核生物，秀丽隐杆线虫和 与祖先相关的原核微生物具有小基因组， 狂热球菌被选为代表性基因组。作为人类cDNA 在NCL赞助的基因组项目中可用，将包括在内 在研究中，最终目标是所有人的结构表征 人类基因组的蛋白质。通过选择原核生物和真核 基因组我们应该能够探索障碍的全部障碍 来自任何基因组的基因产物的高通量结构测定。这 飞行员中心有三个工作组：蛋白质生产组，NMR组和 X射线晶体学组。使用机器人方法，蛋白质产生 小组计划为两个NMR提供大约80个蛋白质/周（每周1-5 mg） 和X射线晶体学研究。虽然NMR组开发了方法 这可能会导致高通量方法，即X射线 晶体学小组已在三个领域开发了创新方法 蛋白质晶体学。它们是：使用微克结晶的蛋白质结晶 样本的数量，数据收集效率提高3至5倍 同步器位点，并使用硫取得突破 异常散射信号。新的结晶过程将 显着影响结构性基因组学本质上所有蛋白质， 即使是可以以微克数量表示的人也将是候选者 晶体学研究。后者在 大规模结构确定的成本效益，因为它可以允许 一个常规解决蛋白质晶体结构而无需 用硒原子代替硫，节省时间和成本。这 建议旨在整合这些发展和其他发展，以生成系统 用于具有成本效益的高通量结构的确定 和真核系统。一旦完全开发，该系统将急剧 改变我们的结构确定速度。它将对 这个国家的医学和生物技术发展。