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，即属于细菌和古细菌的单细胞生物已经发展为防御病毒攻击。这种可继承的机制称为CRISPR系统，存在于许多生物中，其中一些生物会引起动植物的疾病。例如，特征良好的CRISPR属于细菌，这是牙齿腔的主要原因。蛋白质的功能与它们的三维结构直接相关。我们将确定和解释属于CRISPR系统的关键分子机的结构。这种多组分组装策划了在CRISPR研究中的模型有机体中，在sulfolobus solfataricus中策划了病毒RNA的沉默。为此，我们将使用与图像处理结合的电子显微镜。该技术允许获取孤立的组件的投影图像，并使用它们来计算其3D形状，因此提供了对作为病毒攻击的防御的分子机制的重要见解。这项研究在生物学上很重要，因为它是了解大量生物的关键，如何抵消病毒感染。从长远来看，它在生物技术方面也具有强大的潜力，因为它可以被利用为特定针对疾病相关的微生物。这项研究将在爱丁堡的生物科学学院进行，在该学院与生物学科学的合作建立了cormerecorment of Acralla in Compare and storcorce and storcred and storcrew and storcorce and s and storcorn and storcrew and storcorn and s and storcep and storcorce in Comporta and s and storcep and storcep and storcep and s and s and s and sterred and storew and s and s and storred。

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