MRI: Acquisition of Robotics Instrumentation for Crystallization of Biomacromolecules

MRI：获取用于生物大分子结晶的机器人仪器

• 批准号: 0922269
• 负责人: George Richter-Addo
• 金额: $ 35.94万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0922269&HistoricalAwards=false
• 关键词: MRI; Acquisition; Robotics; Instrumentation; Crystallization

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This award will allow structural biologists at the University of Oklahoma-Norman campus to establish an automated Macromolecular Crystallization Core Facility that will enable researchers throughout the State and regionally to accelerate the pace at which diffraction-quality crystals are obtained for X-ray crystallographic studies. This core facility will enhance structural biology research and promote collaborations. In addition to the five research groups at OU, research groups at seven other institutions in Oklahoma seek atomic level insight into the conformational changes associated with macromolecules that regulate cellular biology. Three of these institutions are primarily undergraduate institutions with limited resources for research. This new technology will allow structural biologists in Oklahoma to maintain competitive research programs and educate the next generation of scientists. The new instrumentation will help to reduce the barriers to initiating structural approaches to biological questions and encourage research groups who would otherwise find the initial costs associated with starting crystallization trials for biomacromolecules prohibitively high. This core facility will serve as a focal point for organizing an annual symposium and hosting workshops aimed at enhancing the overall educational and research experiences of undergraduate and graduate students in Oklahoma. A significant number of potential users of the equipment have primarily teaching responsibilities, and the use of this equipment will be incorporated into the undergraduate and graduate biochemistry curriculum. Crystallography is a critical component of interdisciplinary approaches to understanding how changes in structure translate into a change in function. The fluid handling and automated imaging instrumentation that will be acquired with this funding will ease the more difficult and time consuming steps in the discovery process. These instruments will allow researchers to explore more quickly and efficiently many more possible crystallization conditions and thus allow more time to focus effort on interpreting structure-function relationships and designing experiments to test new ideas and hypotheses generated by new crystal structures. These structural biology research efforts will provide new insights into the molecular signals governing enzyme function, metabolism, gene regulation, and cellular responses to environmental change. Proteins and nucleic acids often alter their conformation when binding small molecule substrates such as maltose, adenosine triphosphate, nicotinamide adenine dinucleotide, nitric oxide, or glutathione. For example, researchers will explore how adding a phosphoryl group to a protein or inserting a uracil in an mRNA can change the shape of the biopolymer and thus regulate the timing of its function. When only small amounts of biological samples are available, such as carbohydrate-modified proteins, the new small-volume fluid handling technology will open doors to structural biology inquiries. Results from these studies will be published in peer reviewed journals.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。该奖项将允许俄克拉荷马大学诺曼校区的结构生物学家建立一个自动化的大分子结晶核心设施，使整个国家和地区的研究人员能够加快获得衍射质量晶体用于X射线晶体学研究的步伐。该核心设施将加强结构生物学研究并促进合作。除了麻省理工学院的五个研究小组外，俄克拉荷马州其他七个机构的研究小组也在寻求原子水平上的洞察力，以了解与调节细胞生物学的大分子相关的构象变化。其中三所院校主要是本科院校，研究资源有限。这项新技术将使俄克拉荷马州的结构生物学家能够保持有竞争力的研究项目，并教育下一代科学家。新的仪器将有助于减少生物学问题的结构方法的障碍，并鼓励研究小组，否则他们会发现与生物大分子结晶试验相关的初始成本过高。这一核心设施将作为组织年度研讨会和举办讲习班的协调中心，旨在提高俄克拉荷马州本科生和研究生的整体教育和研究经验。大量的设备的潜在用户有主要的教学责任，使用这种设备将被纳入本科生和研究生的生物化学课程。 晶体学是理解结构变化如何转化为功能变化的跨学科方法的关键组成部分。将用这笔资金购买的流体处理和自动成像仪器将减轻发现过程中更困难和耗时的步骤。这些仪器将使研究人员能够更快、更有效地探索更多可能的结晶条件，从而有更多的时间专注于解释结构-功能关系和设计实验，以测试新晶体结构产生的新想法和假设。这些结构生物学的研究工作将提供新的见解的分子信号管理酶的功能，代谢，基因调控和细胞对环境变化的反应。 蛋白质和核酸在结合小分子底物如麦芽糖、三磷酸腺苷、烟酰胺腺嘌呤二核苷酸、一氧化氮或谷胱甘肽时经常改变它们的构象。例如，研究人员将探索如何在蛋白质中添加磷酰基或在mRNA中插入尿嘧啶可以改变生物聚合物的形状，从而调节其功能的时间。当只有少量的生物样品可用时，如碳水化合物修饰的蛋白质，新的小体积流体处理技术将为结构生物学研究打开大门。 这些研究的结果将发表在同行评审的期刊上。