Community Engagement

社区参与

基本信息

批准号：
10093093
负责人：
RAMA RANGANATHAN
金额：
$ 28.38万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10093093
关键词：
Address Area Automobile Driving Biological Biological Process Biology Book Chapters Book Reviews Catalysis Characteristics Charge Collaborations Communities Complex Computer software Coupled Crystallization Crystallography Data Analyses Disease Educational workshop Elderly Engineering Enzymes Experimental Designs Friends Goals Guidelines Image Interest Group International Journals Knowledge Lasers Measurement Methodology Methods Microfluidics Microspectrophotometry Molecular Molecular Conformation Motion Oral Peer Review Pharmacology Physiologic pulse Physiological Postdoctoral Fellow Process Protein Dynamics Proteins Publishing Reaction Regulation Resolution Roentgen Rays Role Science Scientist Services Signal Transduction Structural Biologist Structure Students Sulfamethoxazole Synchrotrons System Techniques Technology Temperature Therapeutic Time Training Universities Work X ray diffraction analysis X-Ray Crystallography applied biomedical research base beamline biophysical chemistry career chemical reaction community engagement data modeling detector early experience electric field experimental study high school instrumentation interest macromolecule meetings member new technology novel novel strategies posters practical application prospective recruit software development success technology research and development time use tool transmission process undergraduate student web site

项目摘要

Abstract A major goal is biomedical science is to move beyond static images of proteins and other biological macromolecules to the internal dynamics underlying their function. This level of study is necessary to understand how these molecules work, to engineer new functions, and to rationally develop therapeutics. In this application, we propose two technological research and development projects that take advantage of the special characteristics of the BioCARS national synchrotron facility to address these goals. In the first, TR&D 1, we describe time-resolved serial micro-crystallography (TR-SMX) coupled with initiation of chemical reactions within molecules. This approach is enabled by the high intensity and tight focusing of X-rays at BioCARS, the availability of a large area, fast detectors, and the use of novel crystal injectors and microfluidic mixers. TR- SMX enables users to observe the dynamics of molecules as they execute their biological function at physiological temperatures. In the second, TR&D 2, we describe electric field-stimulated X-ray crystallography (EFX), a new method visualizing conformational changes within proteins and other biological macromolecules. This method uses external electric fields to induce global, subtle motions of atoms within proteins, with readout using time-resolved X-ray diffraction. Initial work demonstrates the practical application of EFX, and confirms the ability to globally excite motions throughout a protein molecule, including those of biological relevance. Since charges and dipoles are universally present in macromolecules, EFX represents, in principle, a general approach for intramolecular dynamics. We describe several user-based driving biomedical projects and collaborative and service projects that cover a wide range of important problems and push both technologies. User training and active approaches to dissemination to both expert and non-expert, wider audiences will enable broad use of the new technologies by the scientific community.

抽象的一个主要目标是生物医学科学是超越蛋白质和其他生物学的静态图像大分子对其功能的内部动力学。这种研究水平是必要的了解这些分子如何工作，设计新功能并合理发展治疗疗法。在该应用程序，我们提出了两个利用的技术研发项目生物群体国家同步设施的特殊特征以解决这些目标。在第一个，TR＆D 1，我们描述了时间分辨的串行微结晶（TR-SMX），并结合化学反应的启动在分子中。这种方法是通过在BioCars的X射线强度和紧密聚焦来实现的，大面积，快速检测器以及新型晶体喷油器和微流体混合器的使用。 tr SMX使用户可以在执行其生物学功能时观察分子的动态生理温度。在第二个TR＆D 2中，我们描述了电场刺激的X射线晶体学（EFX），一种新方法，可视化蛋白质和其他生物大分子内的构象变化。该方法使用外部电场来诱导蛋白质中原子的全球，微妙的动作，并带有读数使用时间分辨X射线衍射。最初的工作证明了EFX的实际应用，并确认在蛋白质分子（包括生物学相关性的）中，全球刺激运动的能力。由于大分子中普遍存在电荷和偶极子，因此EFX原则上代表了一般分子内动力学的方法。我们描述了几个基于用户的驾驶生物医学项目和涵盖广泛重要问题并推动这两种技术的协作和服务项目。用户培训和主动方法向专家和非专家传播，更广泛的观众将能够广泛使用科学界的新技术。