Structural characterization of macromolecular assemblies at the atomic level

开发疾病的治疗方法需要了解它们是如何起作用的。例如，我们知道细菌必须穿透细胞膜才能引起感染，但我们对其潜在机制知之甚少。膜的哪一部分是入口点？为什么有些膜是脆弱的，而另一些则不是？通过回答这些问题，我们可以朝着设计能够阻断这些过程的药物迈出第一步。结构生物学通过提供细胞各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，这种方法将细胞成分冷冻，然后用电子轰击，产生样本的图像。尽管这些技术带来了重大发现，但它们所能实现的目标仍有很大的局限性。他们提供的图片通常只是部分的，给我们留下了巨大的知识缺口。我的研究旨在克服这一差距。与伯克贝克学院的电子显微镜小组合作，我开发了计算方法来补充实验技术。该项目专注于三种疾病--肺炎、疱疹和阿尔茨海默氏症--我们使用计算机建模来收集来自各种实验来源的信息，以构建更清晰、更完整的图像，了解这些疾病中关键的细胞成分和过程。

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.