US-Switzerland Collaborative Research on Cryo-Electron Microscopy

该奖项支持耶鲁大学的爱德华·埃格尔曼博士， 与研究中心的雅克·杜博切特博士合作研究， 瑞士洛桑大学电子显微镜。 他们 正在合作研究RecA蛋白， 研究一般基因重组的酶;他们的方法将 也大大有助于改善技术， 大分子结构分析。 埃格尔曼博士是一位 研究无序和柔性大分子的生物药理学家， 特别是RecA蛋白和肌动蛋白。 的传统方法 结构测定，如蛋白质晶体学， 通常这些分子都不成功。 埃格尔曼医生 利用电子计算机图像分析技术 显微照片;他正在为此目的开发一种特殊的设备 在仪器和仪器开发部的支持下， NSF的计划。 他的专长在于图形和 软件开发;他依赖于其他实验室， 电子显微镜照片进行研究。 杜博切特博士开创了 完全水合生物样品的低温电子显微镜方法 标本 世界上只有少数几个实验室 在这一领域，杜博切特博士被认为是 它在大分子成像中的应用。 他会准备冷冻水 RecA和其他动态螺旋系统的电子显微照片， 这将为开发和 证明了埃格尔曼博士的图像处理技术 硬件与软件 他们互补的专业知识和设施 将促进他们在RecA和其他动力学方面的共同研究 蛋白质聚合物，这两个实验室将受益于互惠 转让专门技术。 冷冻的、完全水合的生物标本的电子显微镜 已经成为结构性建筑领域最有前途的新发展之一， 生物学在过去的几年里。 它提供了一个最强大的 用于可视化无序和动态螺旋的方法 蛋白质聚合物 它产生的标本图像很少或没有 脱水、重金属染色或电子导致的损坏或变形 次给药结束 埃格尔曼博士正在开发仪器和程序， 大大加速了电子显微照片的分析，特别是 从静态中提取有关聚合物动力学和功能的信息 图像. 他的计算机辅助增强和重建技术- 对于冷冻的、水合的标本， 传统的电子显微照片，由于对比度弱的问题， 和电子显微镜光学引入的伪影。

This award supports Dr. Edward Egelman of Yale University to collaborate in research with Dr. Jacques Dubochet of the Center for Electron Microscopy of the University of Lausanne, Switzerland. They are collaborating in a study of the RecA protein, the most intensively studied enzyme of general genetic recombination; their approach will also contribute substantially to improving techniques for the structural analysis of macromolecules in general. Dr. Egelman is a biophysicist who studies disordered and flexible macromolecules, specifically the RecA protein and actin. Traditional methods of structure determination, such as protein crystallography, have been generally unsuccessful with these molecules. Dr. Egelman has been examining them using computer-based image analysis of electron micrographs; he is developing a special facility for this purpose with support from the Instrumentation and Instrument Development Program of NSF. His particular expertise lies in graphics and software development; he depends on other laboratories for the electron micrographs to be studied. Dr. Dubochet has pioneered methods of cryo-electron microscopy of fully hydrated biological specimens. Only a handful of laboratories in the world are working in that field, and Dr. Dubochet is considered the leading expert on its use in imaging macromolecules. He will prepare frozen hydrated electron micrographs of RecA and other dynamical helical systems, which will provide one of the best means for both developing and demonstrating the effectiveness of Dr. Egelman's image processing hardware and software. Their complementary expertise and facilities will accelerate their mutual research on RecA and other dynamical protein polymers, and both laboratories will benefit from a reciprocal transfer of specialized techniques. The electron microscopy of frozen, fully hydrated biological specimens has emerged as one of the most promising new developments in structural biology in the past several years. It offers one of the most powerful methods available for visualizing disordered and dynamic helical protein polymers. It produces images of specimens with little or no damage or distortion from dehydration, heavy metal staining or electron dose. Dr. Egelman is developing instruments and programs to allow greatly accelerated analysis of electron micrographs, in particular to extract information about polymer dynamics and function from static images. His techniques for computer-aided enhancement and reconstruc- tion are even more necessary for frozen, hydrated specimens than for conventional electron micrographs, due to the problems of weak contrast and artifacts introduced by the optics of the electron microscope.