Elucidating the molecular architecture of the Archaeal CMR complex, a key player in the unicellular immune response.

我们想要了解一种新发现的机制的细节，即属于细菌和古生菌的单细胞生物已经发展成为抵御病毒攻击的防御机制。这种可遗传的机制被称为CRISPR系统，存在于许多生物体中，其中一些生物体会导致动植物疾病。例如，一个特征良好的CRISPR属于细菌，这是导致龋齿的主要原因。蛋白质的功能与其三维结构直接相关。我们将确定和解释属于CRISPR系统的关键分子机器的结构。这种多组分的组装协调了病毒RNA在Archaeon Sulfolobus solfararicus中的沉默，Sulfolobus solfararicus是CRISPR研究的模式生物。为此，我们将使用电子显微镜与图像处理相结合。这项技术允许获取分离组件的投影图像，并使用它们来计算其3D形状，从而为防御病毒攻击的分子机制提供重要的见解。这项研究具有重要的生物学意义，因为它是了解大量活生物如何对抗病毒感染的关键。从长远来看，它在生物技术方面也有很大的潜力，因为它可以被利用来专门针对与疾病相关的微生物。这项研究将在爱丁堡的生物科学学院进行，该学院最近与圣安德鲁斯的生物医学系合作建立了最先进的结构电子显微镜资源，圣安德鲁斯是古生物分子生物学的卓越中心。

We want to understand the fine detail of a newly discovered mechanism that unicellular organisms belonging to Bacteria and Archaea have developed as a defense from viral attack. This inheritable mechanism, termed CRISPR system, is present in a number of organisms, some of which cause disease in plants and animals. As an example, a well-characterized CRISPR belongs to the bacterium which is the main cause for dental cavities.The function of proteins is directly linked to their three-dimensional structure. We will determine and interpret the structure of a key molecular machine belonging to the CRISPR system. This multi-component assembly orchestrates the silencing of viral RNA in the Archaeon Sulfolobus solfataricus, a model organism in the study of CRISPR. To do so, we will use electron microscopy coupled to image processing. This technique allows to acquire projection images of isolated assemblies, and to use them to calculate their 3D shape, therefore providing important insight on the molecular mechanisms used as defense from viral attack.This study is biologically important because it is the key to understand how a large number of living organisms counteract viral infection. In the longer term, it also has a strong potential in biotechnology, since it could be exploited to specifically target disease-related microorganisms.This research will be performed at the School of Biological Sciences in Edinburgh, where state-of-the-art resources for structural electron microscopy have been recently established, in collaboration with the Biomedical Sciences department in St Andrews, a centre of excellence in the molecular biology of Archaea.