MICA: A super resolution optical microscopy facility at the MRC Laboratory of Molecular Biology.

光学显微镜在现代生物医学研究中起着不可或缺的作用。通过提供在健康和患病细胞内可视化特定过程的能力，通常是实时的，这项技术已经成为增加我们对生物过程知识的推动力。当然，这种知识对于制定诊断和治疗特定人类疾病的新战略至关重要。直到最近，光学显微镜一直受到所谓的“衍射极限”的阻碍。这是显微镜能够分辨出两个物体之间距离的理论限制，通常是在可见光波长的一半范围内（~ 250纳米，或1/4000毫米）。我们细胞内许多重要的生物结构都小于250纳米，因此仍然没有得到很好的表征。这些结构包括执行特定细胞功能的“细胞器”和运输发生的膜结合载体和细丝，以及传染性病毒。在过去的几年里，已经发展了几种显微镜技术，可以绕过衍射极限，从而提供了进入细胞内以前未被认识到的过程的途径。这些“超分辨率”（SR）方法——其中一些方法可以使特定分子的定位精度达到传统显微镜的十倍——有望彻底改变生物医学研究，特别是当与英国已有的其他技术相结合时。剑桥的两个mrc资助的研究机构——分子生物学实验室（LMB）和线粒体生物学单位（MBU）——提议联合建立一个应用超分辨率光学显微镜的多用户创新中心。LMB和MBU的科学家已经并将继续在基础生物过程方面取得重大发现，并经常将其转化为商业和治疗上的成功。在单个蛋白质和蛋白质复合物结构的尺度上以及在细胞水平上研究生物过程有着显著的记录。SR平台将缩小这些分子和细胞研究之间的差距，允许在世界知名的研究环境中对细胞过程及其与疾病的关系进行多尺度分析。光学显微镜对LMB和MBU的关键重要性是由bbbb20高度使用的共聚焦或宽视场显微镜证明的，直到最近，最高质量的光学显微镜可用。随时访问SR显微镜将对组织的生产力产生重大影响。事实上，LMB和MBU中的26个小组都有需要特定SR平台的项目。他们的需求只能通过提供三种不同的，领先的SR系统来满足：结构照明，单分子定位显微镜（例如PALM/STORM）和受激发射损耗（STED）显微镜。这些系统具有不重叠的优势，不同的项目需要不同的系统。大量的附加价值将通过以下方式提供：(i)利用合作伙伴组织内非常成功的研究项目和互补的技术专长，（ii）建立在LMB开发的开创性生物技术基础上，为SR技术开发卓越的标签方法，（iii）与工业伙伴的紧密合作，以及（iv）为其他本地用户提供访问，以促进他们的研究并促进与LMB和MBU的合作。这个项目是可持续的。它建立在完善的显微镜资源管理和用户培训基础设施的基础上，并包括通过建立工业伙伴关系和LMB和MBU的重大财政承诺，尽早获得新的发展。通过提供SR技术培训来培养下一代科学家也是一个重要的组成部分。

Light microscopy plays an indispensable role in modern biomedical research. By providing the ability to visualise specific processes within healthy and diseased cells, often in real-time, this technique has been a driving force in increasing our knowledge of biological processes. This knowledge is, of course, essential for developing new strategies for the diagnosis and treatment of specific human diseases. Until recently, light microscopy has been hampered by the so-called "diffraction limit". This is a theoretical limit to how far two objects need to be apart before they can be resolved by the microscope, and is typically in the region of half the wavelength of visible light (~ 250 nanometers (nm), or 1/4000th of a millimetre). Many important biological structures within our cells are smaller than 250nm and therefore remain poorly characterised. These structures include the "organelles" that perform specific cellular functions and the membrane-bound carriers and filaments along which trafficking occurs, as well as infectious viruses. Several microscopy techniques have been developed in the last few years that allow the diffraction limit to be bypassed, thereby providing access to previously unappreciated processes within cells. These 'super resolution" (SR) methods-some of which allow specific molecules to be localised with a precision of up to ten times greater than conventional microscopy-promise to revolutionise biomedical research, particularly when combined with other techniques in which the UK has pre-established expertise.Two MRC-funded research organisations in Cambridge-the Laboratory of Molecular Biology (LMB) and Mitochondrial Biology Unit (MBU)-are proposing to jointly establish a multi-user centre of innovation in applied super resolution (SR) optical microscopy. Scientists at LMB and MBU have made, and continue to make, major discoveries into fundamental biological processes and have frequently translated them into commercial and therapeutic successes. There is a remarkable track record of studying biological processes at the scale of the structure of individual proteins and protein complexes, as well as at the cellular level. SR platforms would close the gap between these molecular and cellular studies, allowing multi-scale analysis of cellular processes and the relationship to disease in a world-renowned research environment. The critical importance of light microscopy to LMB and MBU is demonstrated by the presence of > 20 highly used confocal or wide-field microscopes, until recently the highest quality optical microscopes available. Ready access to SR microscopy will make a major impact on the productivity of the organisations. Indeed, 26 groups within the LMB and MBU have projects that require specific SR platforms. Their needs can only be fulfilled by providing three different, leading SR systems: structured illumination, single molecule localisation microscopy (e.g. PALM/STORM) and stimulated emission depletion (STED) microscopy. These systems have non-overlapping strengths and different projects require different systems.Substantial added value will be provided by (i) capitalising on the highly successful research programmes and complementary technological expertise within the partner organisations, (ii) building on pioneering biotechnology developed at LMB to develop superior labelling methods for SR techniques, (iii) strong collaborations with industrial partners and (iv) provision of access to other, local users to facilitate their research and foster collaborations with LMB and MBU. The project is sustainable. It builds on well-established infrastructure for management of microscopy resources and user training, and includes early access to new developments through the establishment of industrial partnerships and a significant financial commitment from LMB and MBU. There is also a strong component of cultivating the next generation of scientists by providing training in SR techniques.