STRUCTURAL BIOLOGY--IMAGE PROCESSING OF ELECTRON MICROGRAPHS

本课题利用图像处理技术对电子束进行分析， 显微照片为了回答结构生物学中的重要问题， 为了获得相对高分辨率二维和三维结构 关于生物大分子的信息。 生物样本可以在电子显微镜中使用 许多标本制备技术。冷冻电子显微镜，a 相对较新的技术，试图通过 用一层冰包裹住标本合作研究， LSB、NIAMS目前正在进行一些项目， 电子显微图像被计算校正，组合， 平均、重建或以某种方式计算增强， 提高信噪比或增加可解释性 这些结构被可视化。“冷冻”图像通常较低 对比度和需要更大的计算机处理比传统的 电子显微镜，以达到令人满意的结果。 我们的研究特别感兴趣的是对病毒的理解， 结构.目前，我们正在继续努力调查 一种大型动物病毒，人类单纯疱疹病毒（1型）。我们 正在完成主要衣壳蛋白的定位， 试图获得更高分辨率的结构。生物材料 这些疱疹病毒重建是通过与 弗吉尼亚大学夏洛茨维尔分校的研究， 厄普约翰公司，卡拉马祖在LSB、NIAMS中进行电子显微镜检查。 我们的三维重建的解释是由所有 合作者 在结构生物学方面的其他一些合作项目是 目前正在进行中。我们用三维重建技术来研究 二十面体L-A病毒（来自酵母）、乳头瘤病毒和 脊髓灰质炎病毒。我们比较了完整的（含RNA的）L-A的结构， 病毒与空的L-A病毒。在一项关于乳头瘤病毒的新研究中（ 与NIAMS和NCI的合作），我们已经验证了已知的结构， 牛乳头瘤病毒（bpv），最近获得了3D 重组抗bpv L1蛋白的抗体。我们希望能够 为了定位bpv的两个主要蛋白质， 一些乳头状瘤抗体的功能和活性。

In this project, image processing techniques are used to analyze electron micrographs. To answer important questions in structural biology, it is necessary to obtain relatively high resolution 2- and 3-D structural information about biological macromolecules. Biological specimens can be visualized in the electron microscope using a number of specimen preparation techniques. Cryoelectron microscopy, a relatively new technique, attempts to preserve native structure by surrounding the specimen with a layer of ice. Collaborative studies with LSB, NIAMS are currently under way on a number of projects, whereby electron micrograph images are computationally corrected, combined, averaged, reconstructed, or in some way computationally enhanced to improve the signal-to-noise ratio or to increase the interpretability of the structures being visualized. "Cryo" images are typically lower contrast and require greater computer processing than conventional electron microscopy to achieve satisfactory results. Of particular interest to our research is the understanding of viral structures. At present we are continuing our efforts to investigate the structure of a large animal virus, human herpes simplex virus (type 1). We are completing the localization of the major capsid proteins and attempting to obtain higher resolution structures. Biological material for these herpesvirus reconstructions is provided through a collaboration with researches at the University of Virginia, Charlottesville, and from the Upjohn Co., Kalamazoo. The electron microscopy is performed in LSB, NIAMS. Interpretation of our 3-D reconstructions is performed jointly by all collaborators. A number of other collaborative projects in structural biology are currently in progress. We are using 3-D reconstruction techniques to study the structure of icosahedral L-A virus (from yeast), papillomavirus, and polio virus. We have compared the structures of full (RNA containing) L-A virus with empty L-A virus. In a new study of papillomavirus (in collaboration with NIAMS and NCI), we have verified the known structure of bovine papillomavirus (bpv), and have recently obtained a 3D reconstruction of antibodies to the L1 protein of bpv. We hope to be able to localize the two major proteins of bpv, as well as to understand more of the function and activity of a number of papilloma antibodies.