Structural characterization of macromolecular assemblies at the atomic level

原子水平大分子组装体的结构表征

• 批准号: G0600084/1
• 负责人: Maya Topf
• 金额: $ 80.24万
• 依托单位: Birkbeck, University of London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600084%2F1
• 关键词: Structural; characterization; macromolecular; assemblies; atomic

Developing cures for diseases requires an understanding of how they work. We know, for example, that bacteria must penetrate the membranes of cells to cause infection, but we do not know much about the underlying mechanisms. Which part of the membrane serves as the entry point? Why are some membranes vulnerable while others are not? By answering these kinds of questions, we can take the first steps towards designing drugs capable of blocking these processes. Structural biology aids this project by providing pictures of parts of cells. This is done through the use of experimental techniques such as cryogenic electron microscopy, a method whereby cell components are frozen and then bombarded with electrons, yielding an image of the sample. Though such techniques have led to great discoveries, there are significant limitations to what they can accomplish. The pictures they provide are usually only partial, leaving us with significant gaps in our knowledge. My research aims to overcome this gap. Working with the electron microscopy group at Birkbeck college, I develop computational methods to complement experimental techniques. The project focuses on three diseases-pneumonia, herpes, and Alzheimer‘s-and we use computer modelling to pull together information from a variety of experimental sources to construct clearer and more complete images of the crucial cellular components and processes at work in these diseases.

开发治疗疾病的方法需要了解它们是如何工作的。例如，我们知道细菌必须穿透细胞膜才能引起感染，但我们对潜在的机制知之甚少。膜的哪一部分是进入点？为什么有些细胞膜易受伤害，而另一些则不然？通过回答这些问题，我们可以迈出设计能够阻断这些过程的药物的第一步。结构生物学通过提供细胞部分的图片来帮助这个项目。这是通过使用低温电子显微镜等实验技术来完成的，低温电子显微镜是一种将细胞成分冷冻然后用电子轰击产生样品图像的方法。尽管这些技术带来了重大的发现，但它们所能取得的成就却有很大的局限性。他们提供的图片通常只是部分的，给我们的知识留下了很大的空白。我的研究旨在克服这一差距。与电子显微镜组在伯克贝克学院工作，我开发计算方法，以补充实验技术。该项目聚焦于三种疾病——肺炎、疱疹和阿尔茨海默病——我们使用计算机建模将来自各种实验来源的信息整合在一起，以构建更清晰、更完整的图像，了解在这些疾病中起作用的关键细胞成分和过程。