MICA: Nanoscopy Oxford (NanO): Novel Super-Resolution Imaging Applied to Biomedical Sciences

在过去的十年中，全新的技术已经开发出来，绕过了光学显微镜的限制，使研究人员能够第一次在固定和活细胞中以纳米尺度可视化细胞内结构，细胞表面和细胞外空间。这为研究正常细胞结构和功能创造了全新的可能性。该应用程序的主要目的是充分整合和协调跨牛津校园的多学科小组（生物学家，物理学家，工程师和化学家），开发超分辨率显微镜（SRM），并使其可用于广泛的生物医学界（例如WIMM，邓恩学校，WTCHG，生物化学和DPAG），以产生对正常生物过程的新见解以及这些过程如何在人类疾病中受到干扰。我们建议，这个新的财团被称为Nanoscopy牛津（NanO）。在过去的几年中，一些生物医学研究所和部门在牛津大学已作出承诺，发展成像作为一个关键的基础设施，支持他们的科学计划。此外，这些部门和研究所都有助于在美光倡议的领导下，在牛津成像的总体战略愿景。这使得牛津大学校园能够建立广泛的传统成像，并在开发SRM方面迈出了第一步。招募该领域的科学领导者（例如Davis，Eggeling，Schermelleh）及其与该研究领域的国际领导者（Hell，Sedat，Jakobs）的合作使我们的财团处于有利地位，并进一步投资，成为下一代成像的领先英国和国际中心。认识到没有一种方法适合所有应用，我们将在牛津现有成像设施和相关管理结构的基础上建立，扩展和优化SRM的全方位方法（STED，RESOLFT，3DSIM和PALM/STORM）。此外，我们将调整每种类型的显微镜，以最大限度地提高我们执行纳米级成像的能力，开发多色和三维成像的新方法。我们将通过减少像差、改进活细胞SRM成像的荧光标记来提高厚标本的成像质量，我们将加快成像过程并开发新的方法来分析超分辨图像。通过简化这些技术，我们将把尚未商业化的复杂技术带到SRM经验有限的生物医学研究人员的范围内。该联盟在教学和培训生物医学研究人员使用各种形式的显微镜方面有着完善的计划，因此很有可能成为英国在这一领域的培训设施。实现这一愿景，包括技术开发，采用技术来分析关键的细胞生物学问题，然后将其应用于生物医学问题（完全集成微米和纳米）将使牛津成为下一代显微镜发展及其应用于人类疾病分析的国际卓越中心。

Over the past decade entirely new technologies have been developed that bypass the limits of light microscopy allowing researchers to visualise, for the first time, intracellular structures, the cell surface and the extracellular space at the nanometre scale in both fixed and living cells. This has created entirely new possibilities to investigate normal cell structure and function. The principal aim of this application is to fully integrate and coordinate multidisciplinary groups (biologists, physicists, engineers and chemists) across the Oxford campus, to develop super-resolution microscopy (SRM) and to make this available to a broad biomedical community (e.g. WIMM, Dunn School, WTCHG, Biochemistry and DPAG) to generate new insights into normal biological processes and how these are perturbed in human diseases. We propose that this new consortium is called Nanoscopy Oxford (NanO).Over the past few years several biomedical institutes and Departments in Oxford have made commitments to developing imaging as a key infrastructure for supporting their scientific programmes. In addition these departments and institutes have contributed to an overarching strategic vision for imaging in Oxford under the leadership of the Micron initiative. This has enabled the Oxford campus to establish a wide range of conventional imaging and to take the first steps in developing SRM. Recruitment of scientific leaders in this area (e.g. Davis, Eggeling, Schermelleh) and their collaborations with international leaders in this area of research (Hell, Sedat, Jakobs) have placed our consortium in strong position, with further investment, to become a leading UK and international centre for next generation imaging. Recognising that no single approach is suitable for all applications, we will build upon current imaging facilities and associated management structures in Oxford to establish, extend and optimise the full range of approaches to SRM (STED, RESOLFT, 3DSIM and PALM/STORM). Furthermore, we will adapt each type of microscopy to maximise our ability to perform nanoscale imaging, developing new approaches for multi-colour and three-dimensional imaging. We will improve the quality of imaging in thick specimens by reducing aberrations, improving fluorescent labels for live-cell SRM imaging, and we will speed up the imaging process and develop new methods for analysis of the super-resolved images. By streamlining these techniques we will bring complex technologies, not yet commercialised, within the reach of biomedical researchers with limited experience of SRM. The consortium has well established programmes in teaching and training biomedical researchers in the use of all forms of microscopy and therefore is well placed to become a training facility for the UK in this area. Realising this vision including technical development, adoption of techniques to analyse key cell biological questions and then applying them to biomedical issues (fully integrating Micron and NanO) will make Oxford an international centre of excellence in the development of next generation microscopy and its application to the analysis of human disease.