Super Resolution Imaging for Cell Biology and Neuroscience at UCL

伦敦大学学院细胞生物学和神经科学超分辨率成像

• 批准号: MR/K015826/1
• 负责人: Mark Marsh
• 金额: $ 205.43万
• 依托单位: University College London
• 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=MR%2FK015826%2F1
• 关键词: Super; Resolution; Imaging; Cell; Biology

Microscopy has been one of the principle tools for discovery-based research at the cell and molecular level, allowing insights to the organisation and dynamics of cells, as well as the faults associated with infection and disease. Over the last 25 years increasingly sophisticated microscopes, together with new experimental tools such as fluorescent protein tags, improved lasers and cameras, and developments in live cell imaging, have led to rapid advances in our understanding of cell organisation and function. Nevertheless, imaging at high resolution is limited by the properties of light to ~250 nm, meaning that information at the level of molecules and molecular complexes cannot be obtained using conventional light microscopes. Thus, high-resolution studies have been restricted to electron microscopy (EM), which can only be used on fixed and highly processed samples, and has limited capacity to identify specific molecular components. In recent years several novel optical and computational approaches have been developed to break the diffraction-limit of conventional light microscopy, with the potential to obtain molecular/structural information at significantly higher resolution (approx. 2-20 fold improvement). By combining multiple fluorescently-labelled probes, within the same sample, together with live cell imaging, these so-called super-resolution nanoscopy techniques are able to bridge the current technologies of diffraction-limited microscopy and EM to generate new detailed molecular and mechanistic insights into the cellular and molecular processes that underlie normal cell function and disease.Super-resolution imaging (SRI) instruments are now becoming commercially available allowing cellular biomedical researchers to begin to apply these exciting new technologies to a multitude of questions in cell biology, neurobiology, infectious disease and many other fields of biomedical research. Development is still at an early stage and there remain many opportunities for progress, particularly in live cell imaging, probe development, software development, analytical tools, etc. However, SRI instruments and technical developers are needed now to work in close collaboration with biomedical researchers to establish the technology and push instrument and application development.This application will link MRC-funded scientists in the Cell Biology Unit/Laboratory for Molecular Cell Biology (CBU/LMCB) and Prion Unit (MRC PU), as well as the MRC/UCL Centre in Molecular Medical Virology (MRC CMMV), with members of UCL's Faculties of Life Sciences, Medicine and Brain Sciences, the London Centre for Nanotechnology (LCN), UCL physicists and chemists, computer scientists, image-based bio-informaticians and the National Physics Laboratory Teddington (NPL), to establish and develop platforms for SRI. The facility will be centred on commercial off-the-shelf SRI instruments that will provide a benchmark against which UCL and NPL members of the programme will develop new systems and instruments optimised for biomedical research. The facility will also provide capacity-building opportunities for students and postdoctoral fellows to train/work at the interface of biology, imaging and instrument development. Together this presents a timely window of opportunity in which to build on UCL's excellent imaging facilities and world leading biomedical research community to create a cutting edge, interactive SRI research and development programme for application to biomedical research.

显微镜一直是细胞和分子水平上基于发现的研究的主要工具之一，可以洞察细胞的组织和动态，以及与感染和疾病相关的缺陷。在过去的 25 年里，日益复杂的显微镜，加上荧光蛋白标签、改进的激光器和相机等新的实验工具，以及活细胞成像的发展，使我们对细胞组织和功能的理解迅速进步。然而，高分辨率成像受到~250 nm 光特性的限制，这意味着使用传统光学显微镜无法获得分子和分子复合物水平的信息。因此，高分辨率研究仅限于电子显微镜（EM），它只能用于固定和高度加工的样品，并且识别特定分子成分的能力有限。近年来，已经开发出几种新颖的光学和计算方法来打破传统光学显微镜的衍射极限，有可能以更高的分辨率（大约提高 2-20 倍）获得分子/结构信息。通过在同一样本中结合多个荧光标记探针以及活细胞成像，这些所谓的超分辨率纳米显微镜技术能够连接当前的衍射极限显微镜和电子显微镜技术，从而对构成正常细胞功能和疾病的细胞和分子过程产生新的详细的分子和机制见解。超分辨率成像（SRI）仪器现在正在成为 商业化使细胞生物医学研究人员能够开始将这些令人兴奋的新技术应用于细胞生物学、神经生物学、传染病和许多其他生物医学研究领域的众多问题。发展仍处于早期阶段，仍有许多进步机会，特别是在活细胞成像、探针开发、软件开发、分析工具等方面。然而，SRI 仪器和技术开发人员现在需要与生物医学研究人员密切合作，建立技术并推动仪器和应用程序开发。该应用程序将连接 MRC 资助的细胞生物学单位/分子细胞生物学实验室 (CBU/LMCB) 和朊病毒单位 (MRC) 的科学家。 PU) 以及 MRC/UCL 分子医学病毒学中心 (MRC CMMV) 以及伦敦大学学院生命科学、医学和脑科学学院、伦敦纳米技术中心 (LCN)、伦敦大学学院物理学家和化学家、计算机科学家、基于图像的生物信息学家和国家物理实验室特丁顿 (NPL) 的成员，共同建立和开发 SRI 平台。该设施将以商业现成的 SRI 仪器为中心，该仪器将为 UCL 和 NPL 项目成员开发针对生物医学研究优化的新系统和仪器提供基准。该设施还将为学生和博士后研究员提供在生物学、成像和仪器开发领域进行培训/工作的能力建设机会。这提供了一个及时的机会之窗，可以利用伦敦大学学院优秀的成像设施和世界领先的生物医学研究社区来创建尖端的、交互式的 SRI 研究和开发项目，以应用于生物医学研究。

项目成果

Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response.

• DOI: 10.1371/journal.ppat.1010614
• 发表时间: 2022-07
• 期刊: PLoS pathogens
• 影响因子: 6.7

Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis.

• DOI: 10.1038/ncomms12111
• 发表时间: 2016-07-20
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Banushi B;Forneris F;Straatman-Iwanowska A;Strange A;Lyne AM;Rogerson C;Burden JJ;Heywood WE;Hanley J;Doykov I;Straatman KR;Smith H;Bem D;Kriston-Vizi J;Ariceta G;Risteli M;Wang C;Ardill RE;Zaniew M;Latka-Grot J;Waddington SN;Howe SJ;Ferraro F;Gjinovci A;Lawrence S;Marsh M;Girolami M;Bozec L;Mills K;Gissen P
• 通讯作者: Gissen P

Correction: Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain.

更正：Bat IFITM3 限制取决于 S-棕榈酰化和 CD225 结构域内的多态性位点。

• DOI: 10.26508/lsa.202000747
• 发表时间: 2020
• 期刊: Life science alliance
• 影响因子: 4.4
• 作者: Benfield CT

Assessing the effects of mitofusin 2 deficiency in the adult heart using 3D electron tomography.

• DOI: 10.14814/phy2.13437
• 发表时间: 2017-09
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Beikoghli Kalkhoran S;Hall AR;White IJ;Cooper J;Fan Q;Ong SB;Hernández-Reséndiz S;Cabrera-Fuentes H;Chinda K;Chakraborty B;Dorn GW 2nd;Yellon DM;Hausenloy DJ
• 通讯作者: Hausenloy DJ

Tetherin restricts herpes simplex virus 1 and is antagonized by glycoprotein M.

• DOI: 10.1128/jvi.02250-13
• 发表时间: 2013-12
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Blondeau C;Pelchen-Matthews A;Mlcochova P;Marsh M;Milne RS;Towers GJ
• 通讯作者: Towers GJ