The Opera Phenix Microscope for High Content Screening Applications

用于高内涵筛选应用的 Opera Phoenix 显微镜

• 批准号: BB/R013799/1
• 负责人: Julian Downward
• 金额: $ 30.07万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR013799%2F1
• 关键词: Opera; Phenix; Microscope; Content; Screening

The Crick is a partnership between the Medical Research Council, Cancer Research UK, the Wellcome Trust and three leading universities: UCL (University College London), Imperial College London and King's College London. The Crick aspires to be one of the world's leading medical research institutes. The Crick achieves operational and research efficiencies and economies-of-scale through centralised facilities and functions, known as Science Operations, that provide all researchers at the Crick, irrespective of affiliation, with access to cutting-edge equipment, animals for research and laboratory enabling functions such as the High Throughput Screening facility (HTS).Technical advances mean that it is now commonplace to be able to identify when genes have been altered or lost as part of ageing or a disease process. It is less obvious what effect this loss has on any individual cell and how it contributes to a disease. Indeed, understanding the functional roles for any gene in any particular cell or condition or how any gene normally contributes to the way a cell behaves or responds is still somewhat lacking. Fortunately, we now have reagents (called CRISPRs) that allow researchers to inactivate any gene of interest and assess the consequences of its loss on cell behaviour. The effect of gene loss on the cell is inferred from quantitative analysis of images taken of the cells when they are either growing and moving normally or when they have been challenged to respond to a stimulus. By measuring the properties of cells lacking a single gene, researchers can infer something about the role it might be playing in the cell as a whole. The HTS facility at the Crick has created a system that allows researchers to study the effect of gene loss on cell behaviour for hundreds to thousands of genes simultaneously, experiments referred to as screening.This proposal is for a microscope capable of automatically imaging and analysing the tens of thousands of samples that such experiments demand. This new microscope in conjunction with the CRISPR reagents gives us the opportunity to shed light on both the basic mechanisms of how genes control what cells do and potentially the role they play in important human diseases.

Crick是医学研究委员会、英国癌症研究中心、惠康信托基金和三所顶尖大学：伦敦大学学院、伦敦帝国理工学院和伦敦国王学院的合作伙伴。克里克立志成为世界领先的医学研究机构之一。克里克通过被称为科学操作的中央设施和功能，实现了操作和研究效率以及规模经济，这些设施和功能为克里克的所有研究人员提供了访问尖端设备、用于研究的动物和实验室功能(如高通量筛查设施(HTS))的机会。技术进步意味着现在能够识别基因在衰老或疾病过程中发生改变或丢失的情况已司空见惯。这种缺失对单个细胞有什么影响，以及它是如何导致疾病的，还不太明显。事实上，了解任何基因在任何特定细胞或条件下的功能作用，或者任何基因通常如何影响细胞的行为或反应，仍然有些欠缺。幸运的是，我们现在有了试剂(称为CRISPR)，可以让研究人员使任何感兴趣的基因失活，并评估其丢失对细胞行为的影响。基因缺失对细胞的影响是通过对细胞正常生长和运动时或受到刺激时的图像进行定量分析得出的。通过测量缺乏单个基因的细胞的特性，研究人员可以推断它在整个细胞中可能扮演的角色。位于克里克的HTS实验室已经创建了一个系统，允许研究人员同时研究基因丢失对数百到数千个基因细胞行为的影响，这一实验被称为筛选。这项提议是为了研制一种能够自动成像和分析此类实验所需的数万个样本的显微镜。这一新的显微镜与CRISPR试剂相结合，使我们有机会阐明基因如何控制细胞功能的基本机制，以及它们在人类重要疾病中可能扮演的角色。

项目成果

Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains.

• DOI: 10.7554/elife.69317
• 发表时间: 2021-07-29
• 期刊: eLife
• 影响因子: 7.7
• 作者: Faulkner N;Ng KW;Wu MY;Harvey R;Margaritis M;Paraskevopoulou S;Houlihan C;Hussain S;Greco M;Bolland W;Warchal S;Heaney J;Rickman H;Spyer M;Frampton D;Byott M;de Oliveira T;Sigal A;Kjaer S;Swanton C;Gandhi S;Beale R;Gamblin SJ;McCauley JW;Daniels RS;Howell M;Bauer D;Nastouli E;Kassiotis G
• 通讯作者: Kassiotis G

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase.

• DOI: 10.1042/bcj20210219
• 发表时间: 2021-07-16
• 期刊: The Biochemical journal
• 作者: Basu S;Mak T;Ulferts R;Wu M;Deegan T;Fujisawa R;Tan KW;Lim CT;Basier C;Canal B;Curran JF;Drury LS;McClure AW;Roberts EL;Weissmann F;Zeisner TU;Beale R;Cowling VH;Howell M;Labib K;Diffley JFX
• 通讯作者: Diffley JFX

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase.

• DOI: 10.1042/bcj20210200
• 发表时间: 2021-07-16
• 期刊: The Biochemical journal
• 作者: Bertolin AP;Weissmann F;Zeng J;Posse V;Milligan JC;Canal B;Ulferts R;Wu M;Drury LS;Howell M;Beale R;Diffley JFX
• 通讯作者: Diffley JFX

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp15 endoribonuclease.

• DOI: 10.1042/bcj20210199
• 发表时间: 2021-07-16
• 期刊: The Biochemical journal
• 作者: Canal B;Fujisawa R;McClure AW;Deegan TD;Wu M;Ulferts R;Weissmann F;Drury LS;Bertolin AP;Zeng J;Beale R;Howell M;Labib K;Diffley JFX
• 通讯作者: Diffley JFX