MRI: Acquisition of Robotics Instrumentation for Crystallization of Biomacromolecules

该奖项由2009年《美国复苏和再投资法案》(Public Law 111-5)资助。该奖项将允许俄克拉荷马大学诺曼分校的结构生物学家建立自动化的大分子结晶核心设施，使全州和地区的研究人员能够加快为X射线结晶学研究获得衍射级晶体的步伐。这一核心设施将加强结构生物学研究并促进合作。除了俄克拉何马州大学的五个研究小组外，俄克拉何马州其他七个机构的研究小组寻求原子水平的洞察，以了解与调节细胞生物学的大分子相关的构象变化。这些机构中有三个主要是本科生机构，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研究项目的竞争力，并培养下一代科学家。新的仪器将有助于降低启动生物学问题结构方法的障碍，并鼓励研究小组，否则他们会发现启动生物大分子结晶试验的初始成本高得令人望而却步。这一核心设施将作为举办年度研讨会和举办研讨会的中心，旨在加强俄克拉荷马州本科生和研究生的整体教育和研究经验。该设备的大量潜在用户主要承担教学责任，该设备的使用将纳入本科生和研究生的生物化学课程。结晶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。用这笔资金将获得的流体处理和自动化成像仪器将减轻发现过程中更困难和更耗时的步骤。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，以检验新晶体结构产生的新想法和假设。这些结构生物学研究工作将为控制酶功能、新陈代谢、基因调控和细胞对环境变化的反应的分子信号提供新的见解。蛋白质和核酸在与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结合时，通常会改变其构象。例如，研究人员将探索在蛋白质中添加磷酸基或在mRNA中插入尿嘧啶如何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本可用时，例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议的期刊上。

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.