SHeffield IMAging (SHIMA)

谢菲尔德影像学 (SHIMA)

• 批准号: MR/K015753/1
• 负责人: Simon J. Foster
• 金额: $ 158.05万
• 依托单位: University of Sheffield
• 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%2FK015753%2F1
• 关键词: SHeffield; IMAging; SHIMA

Imaging has been at the heart of huge leaps in understanding in biology and medicine, from the discovery of bacteria using the first microscopes to neuroimaging to determine brain function. All the advances have been totally dependent on the development of new technologies. This is particularly so for the study of objects too small to be seen by the naked eye, where microscopes are essential. Elucidating how cells function, whether they be from humans, plants, fungi or bacteria requires the ability to be able to see the components that make up the cell, determine their localisation and establish how they move relative to each other. In particular this has been driven by developments in microscopy coupled with the use of probes to fluorescently label molecules inside cells and so be able to localise and track them, giving key insights into processes such as cell division, growth and differentiation. However traditional optical microscopy approaches are limited in resolution to about 200 nm, which prevents the nanoscale visualisation of the myriad smaller structures and processes within the cell. Only very recently have new super-resolution (SR) microscopy approaches been invented to allow resolution down to single molecules. Thus we are at a tipping point, where existing methods and levels of understanding will become rapidly superseded by new approaches. In Sheffield we have been quick to recognise the potential of this opportunity and we are at the forefront of the development of new methods in SR microscopy. This includes building our own microscopes, coupling fluorescence microscopy with other high-resolution approaches and applying these advances to important biological and biomedical questions. We are thus ideally placed to optimally exploit the new SR technology as part of a programme of development integrated with application. The University of Sheffield (UoS) is a well-established centre with great strengths in many aspects of biomedical and biological research that are poised to reap the benefits from the new SR technologies. We propose to establish a world-class centre in SR imaging, entitled Sheffield Imaging (SHIMA), based on our current strengths, the proposed project and a large strategic investment by the University of Sheffield. We will purchase commercial SR systems for both Structured Illumination Microscopy (SIM) and Stochastic Optical Reconstruction Microscopy (STORM) as complementary systems allowing single molecule resolution and live cell imaging. The equipment will be housed in our Light Microscopy Facility (LMF) to allow multiple user access from the outset. SR is an emerging field and so an imaging, development centre will be established to drive forward technological advances, for transfer to the LMF. To enhance technology development we will conduct specific seed projects to produce novel probes for both SIM and STORM, to increase the versatility of the techniques and to increase the speed of STORM to allow live cell imaging in 3D. With commercial partners we will ensure the rapid translation of our developments for the community. An interdisciplinary team will manage SHIMA, ensuring optimal technology development within the context of its direct application. Two SHIMA senior experimental officers (SEOs) will be responsible for interdisciplinary technology development, production of novel probes and establishment of widespread biomedical applications. The SEOs will be responsible for training of users, both internal and external creating a vibrant atmosphere of expert researchers across the University (and beyond) with a seamless interface between technology development and application via the LMF. The UoS is committed to SHIMA not only by a substantial direct investment in the project but also via a wider initiative in imaging to establish Sheffield as a key international centre in SR imaging.

成像一直是生物学和医学领域巨大飞跃的核心，从使用第一台显微镜发现细菌到通过神经成像确定大脑功能。所有的进步都完全依赖于新技术的发展。对于肉眼看不见的小物体的研究尤其如此，显微镜是必不可少的。阐明细胞的功能，无论它们是来自人类，植物，真菌还是细菌，都需要能够看到组成细胞的成分，确定它们的定位并确定它们如何相对于彼此移动。特别是，这是由显微镜的发展以及使用探针荧光标记细胞内的分子所推动的，因此能够定位和跟踪它们，从而对细胞分裂，生长和分化等过程提供关键见解。然而，传统的光学显微镜方法的分辨率仅限于约200 nm，这阻止了细胞内无数较小结构和过程的纳米级可视化。直到最近才发明了新的超分辨率（SR）显微镜方法，以允许分辨率下降到单个分子。因此，我们正处于一个临界点，现有的方法和理解水平将迅速被新的方法所取代。在谢菲尔德，我们已经迅速认识到这一机会的潜力，我们处于SR显微镜新方法开发的最前沿。这包括建立我们自己的显微镜，将荧光显微镜与其他高分辨率方法相结合，并将这些进展应用于重要的生物和生物医学问题。因此，我们处于理想的位置，以最佳方式利用新的SR技术，作为与应用相结合的开发计划的一部分。谢菲尔德大学（UoS）是一个成熟的中心，在生物医学和生物研究的许多方面都具有很大的优势，有望从新的SR技术中获益。我们建议建立一个世界级的SR成像中心，名为谢菲尔德成像（SHIMA），基于我们目前的优势，拟议的项目和谢菲尔德大学的大规模战略投资。我们将为结构照明显微镜（SIM）和随机光学重建显微镜（STORM）购买商业SR系统，作为允许单分子分辨率和活细胞成像的互补系统。这些设备将被安置在我们的光学显微镜设施（LMF）中，以便从一开始就允许多个用户访问。SR是一个新兴领域，因此将建立一个成像开发中心，以推动技术进步，并将其转移到LMF。为了加强技术开发，我们将开展特定的种子项目，为SIM和STORM生产新型探针，提高技术的通用性，并提高STORM的速度，以实现3D活细胞成像。与商业合作伙伴一起，我们将确保我们的发展迅速转化为社区。一个跨学科的团队将管理SHIMA，确保在其直接应用的背景下进行最佳技术开发。两名SHIMA高级实验官员（SEO）将负责跨学科技术开发，新型探针的生产和广泛的生物医学应用的建立。SEO将负责内部和外部用户的培训，在整个大学（及其他地区）创造一个充满活力的专家研究人员氛围，通过LMF实现技术开发和应用之间的无缝接口。UoS致力于SHIMA，不仅对该项目进行了大量直接投资，而且还通过更广泛的成像倡议，将谢菲尔德建立为SR成像的主要国际中心。

项目成果

Repurposing a photosynthetic antenna protein as a super-resolution microscopy label.

• DOI: 10.1038/s41598-017-16834-z
• 发表时间: 2017-12-01
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Barnett SFH;Hitchcock A;Mandal AK;Vasilev C;Yuen JM;Morby J;Brindley AA;Niedzwiedzki DM;Bryant DA;Cadby AJ;Holten D;Hunter CN
• 通讯作者: Hunter CN

SosA inhibits cell division in Staphylococcus aureus in response to DNA damage

SosA 抑制金黄色葡萄球菌响应 DNA 损伤的细胞分裂

• DOI: 10.1101/364299
• 发表时间: 2018
• 作者: Bojer M

Human skin commensals augment Staphylococcus aureus pathogenesis.

• DOI: 10.1038/s41564-018-0198-3
• 发表时间: 2018-08
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Boldock E;Surewaard BGJ;Shamarina D;Na M;Fei Y;Ali A;Williams A;Pollitt EJG;Szkuta P;Morris P;Prajsnar TK;McCoy KD;Jin T;Dockrell DH;van Strijp JAG;Kubes P;Renshaw SA;Foster SJ
• 通讯作者: Foster SJ

Complete enzyme set for chlorophyll biosynthesis in Escherichia coli.

大肠杆菌中叶绿素生物合成的完整酶。

• DOI: 10.1126/sciadv.aaq1407
• 发表时间: 2018-01
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Chen GE;Canniffe DP;Barnett SFH;Hollingshead S;Brindley AA;Vasilev C;Bryant DA;Hunter CN
• 通讯作者: Hunter CN

Typhoid toxin hijacks Wnt5a to establish host senescence and Salmonella infection

• DOI: 10.1016/j.celrep.2023.113181
• 发表时间: 2023-10-04
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Elghazaly，Mohamed;Collins，Mark O.;Humphreys，Daniel
• 通讯作者: Humphreys，Daniel