MRI: Acquisition of Robotics Instrumentation for Crystallization of Biomacromolecules

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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.