MRIConsortium: Collaborative Development of Sample Delivery Instrument for Femtosecond Diffraction Studies

斯坦福大学和加州大学弗朗西斯科分校（UCSF）获得了一项奖项，以开发一种用于结构生物学的多功能和优化的样品输送仪器，该仪器将最佳利用SLAC国家加速器实验室（SLAC）的Linac相干光源（LCLS）的独特功能，这是世界上第一个硬X射线自由电子激光器（XFEL）。 它将为整个科学界提供一个新的资源，以研究结构生物学中极具挑战性的问题。通过以原子分辨率或接近原子分辨率对生物分子的结构和动力学进行成像，该仪器有望实现突破，从解开我们细胞如何通信和发育的秘密，到药物发现和新疫苗的开发。该仪器将通过同行评审获得，并向任何结构生物学家开放，包括国内或国际非博士生。和/或少数民族服务机构，谁具有挑战性的大分子结构项目。一个仪器联盟将利用斯坦福大学、SLAC和UCSF提供的教育项目，提供与仪器开发和研究应用相关的实习机会。 这包括一些面向本科生的方案，中学教师方案和两个完善的高中生实习方案。该联盟将为本科生组织培训计划，硕士。和博士学生，博士后和研究人员谁是新的XFEL研究和飞秒衍射研究。通过让更广泛的受众接触最先进的成像工具和LCLS XFEL提供的尖端研究机会，这些机会将通过在职业生涯早期阶段的曝光和参与吸引学生进入科学，技术，工程和数学（STEM）领域。 该仪器将是安装在LCLS的大分子飞秒晶体学（MFX）光束线上的用户设施，并与新兴的飞秒晶体学技术一起使用，该技术已显示出快速发展和巨大的前景，以扩大我们对生物大分子结构和功能的了解。拟议的仪器将大大提高LCLS科学用户社区的能力，通过扩大LCLS晶体学实验的实验选项，进行前沿的结构生物学研究。 它将开辟从具有挑战性的生物靶点的非常小，精致和辐射敏感的晶体中收集有用数据的可能性，包括膜蛋白和供应有限的蛋白质，DNA和RNA的大型复合物，迄今为止尚未进行结构表征。短脉冲长度和高峰亮度的XFEL源可以减轻辐射损伤，并使数据收集的晶体只有几个微米或更小的尺寸，实验不可能在同步加速器光束线。该仪器还将能够确定催化精确的活性位点结构，以高分辨率的敏感金属酶，快速进行同步加速器X射线源的辐射化学。此外，用于这些实验的短（数十fs）X射线脉冲将提供比目前使用同步加速器快两到三个数量级的时域，以增强对生化反应过程的时间分辨结构研究。这些实验能力是独一无二的，至少在美国是这样，世界领先。

An award is made to Stanford University and The University of California, San Francisco (UCSF) to develop a versatile and optimized sample delivery instrument for structural biology that will make optimal use of the unique capabilities at the Linac Coherent Light Source (LCLS), the world's first hard-X-ray Free Electron Laser (XFEL), at SLAC National Accelerator Laboratory (SLAC). It will deliver a new resource available to the entire science community to study extremely challenging problems in structural biology. By imaging the structure and dynamics of biological molecules, at or near atomic resolution, the instrument promises breakthroughs, from unlocking the secrets of how our cells communicate and develop, to drug discovery and development of new vaccines. Access to the instrument will be through peer-review and open to any structural biologists, nationally or internationally including those from non-Ph.D. and/or minority-serving institutions, who have challenging macromolecular structure projects. An instrument consortium will tap into educational programs offered at Stanford, SLAC and UCSF to provide internship opportunities related to the development and research applications of the instrument. This includes a number of programs geared towards undergraduates, programs for secondary school teachers and two well-established internship programs for high school students. The consortium will organize training programs for undergraduate students, M.S. and Ph.D. students, postdocs, and researchers who are new to XFEL research and femtosecond diffraction studies. By exposing a broader audience to the most state-of-the-art imaging tools and the cutting-edge research opportunities enabled by the LCLS XFEL, these opportunities will attract students into Science, Technology, Engineering, and Mathematics (STEM) fields through exposure and engagement at early stages of their careers. The instrument will be a user facility installed on the Macromolecular Femtosecond Crystallography (MFX) beamline at LCLS and used with the emerging technique of femtosecond crystallography, which has shown rapid development and great promise to expand our knowledge of the structure and function of biological macromolecules. The proposed instrument will substantially enhance the capability for the LCLS scientific user community to conduct leading-edge structural biology research by expanding the experimental options for crystallography experiments at LCLS. It will open up the possibility to collect useful data from very small, delicate and radiation sensitive crystals of challenging biological targets, including membrane proteins and large complexes of proteins, DNAs and RNAs in limited supply, that have thus far eluded structural characterization. The short pulse length and high peak brilliance of XFEL sources can mitigate radiation damage, and enable data collection from crystals of only a few microns or smaller in size, experiments not possible at synchrotron beamlines. The instrument will also enable the determination of catalytically accurate active-site structures to high resolution of sensitive metalloenzymes that quickly undergo radiation chemistry at synchrotron x-ray sources. Furthermore, the short (tens of fs) x-ray pulses used for these experiments will provide access to a time domain two-to-three orders of magnitude faster than currently accessible using synchrotrons, for enhanced time-resolved structural studies of biochemical reaction processes. These experimental capabilities are unique, at least in the U.S., and world leading.