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

阐明古菌 CMR 复合体的分子结构，该复合体是单细胞免疫反应的关键参与者。

基本信息

批准号：
BB/J005673/1
负责人：
Laura Spagnolo
金额：
$ 45.78万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ005673%2F1
关键词：
Elucidating molecular architecture Archaeal CMR

项目摘要

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.

我们想了解一种新发现的机制的细节，这种机制是属于细菌和细菌的单细胞生物体发展起来的，作为对病毒攻击的防御。这种可遗传的机制，称为CRISPR系统，存在于许多生物体中，其中一些会导致植物和动物的疾病。例如，一种被充分表征的CRISPR属于细菌，而细菌是导致蛀牙的主要原因。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。这种多组分组装协调了CRISPR研究中的模式生物Sulfolobus solfataricus中病毒RNA的沉默。为此，我们将使用电子显微镜结合图像处理。这项技术可以获得孤立的组件的投影图像，并使用它们来计算它们的3D形状，因此提供了重要的洞察用于防御病毒攻击的分子机制。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体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，因为它可以被用来专门针对与疾病有关的微生物。这项研究将在爱丁堡生物科学学院进行，那里最近建立了最先进的结构电子显微镜资源，与圣安德鲁斯生物医学科学系合作，一个卓越的分子生物学研究中心。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structure of the CRISPR interference complex CSM reveals key similarities with cascade.

DOI：
10.1016/j.molcel.2013.08.020
发表时间：
2013-10-10
期刊：
MOLECULAR CELL
影响因子：
16
作者：
Rouillon, Christophe;Zhou, Min;Zhang, Jing;Politis, Argyris;Beilsten-Edmands, Victoria;Cannone, Giuseppe;Graham, Shirley;Robinson, Carol V.;Spagnolo, Laura;White, Malcolm F.
通讯作者：
White, Malcolm F.

Structure of the Saccharolobus solfataricus type III-D CRISPR effector.

DOI：
10.1016/j.crstbi.2023.100098
发表时间：
2023
期刊：
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
影响因子：
2.8
作者：
Cannone, Giuseppe;Kompaniiets, Dmytro;Graham, Shirley;White, Malcolm F;Spagnolo, Laura
通讯作者：
Spagnolo, Laura

Structure of an octameric form of the minichromosome maintenance protein from the archaeon Pyrococcus abyssi.

DOI：
10.1038/srep42019
发表时间：
2017-02-08
期刊：
Scientific reports
影响因子：
4.6
作者：
Cannone G;Visentin S;Palud A;Henneke G;Spagnolo L
通讯作者：
Spagnolo L

Photobacterium profundum under pressure: a MS-based label-free quantitative proteomics study.

DOI：
10.1371/journal.pone.0060897
发表时间：
2013
期刊：
PloS one
影响因子：
3.7
作者：
Le Bihan T;Rayner J;Roy MM;Spagnolo L
通讯作者：
Spagnolo L

Crystal structures of malonyl-coenzyme A decarboxylase provide insights into its catalytic mechanism and disease-causing mutations.

DOI：
10.1016/j.str.2013.05.001
发表时间：
2013-07-02
期刊：
STRUCTURE
影响因子：
5.7
作者：
Froese, D. Sean;Forouhar, Farhad;Tran, Timothy H.;Vollmar, Melanie;Kim, Yi Seul;Lew, Scott;Neely, Helen;Seetharaman, Jayaraman;Shen, Yang;Xiao, Rong;Acton, Thomas B.;Everett, John K.;Cannone, Giuseppe;Puranik, Sriharsha;Savitsky, Pavel;Krojer, Tobias;Pilka, Ewa S.;Kiyani, Wasim;Lee, Wen Hwa;Marsden, Brian D.;von Delft, Frank;Allerston, Charles K.;Spagnolo, Laura;Gileadi, Opher;Montelione, Gaetano T.;Oppermann, Udo;Yue, Wyatt W.;Tong, Liang
通讯作者：
Tong, Liang