Multidisciplinary Super Resolution Microscopy Facility at Nottingham University

多年来，共聚焦激光扫描显微镜的分辨率一直存在差距，即使有完美的透镜，最佳的对准和大的数值孔径，这种形式的光学显微镜的光学分辨率也被限制在所用光波长的大约一半，这意味着只有细胞结构和至少200到350纳米的物体才能被分辨为不同的独立结构。然而，细胞的许多基本生物学，发生在几十到几百纳米大小范围内的微分子复合物水平上，也就是说，超出了传统光学显微镜的范围。超分辨率显微镜（SRM）的发展突破或绕过经典的衍射极限，将光学分辨率降低到大分子甚至分子水平。它可以精确定位到20纳米的单个分子。SRM还可以提供粒子跟踪，以跟踪样品中的单个分子，例如蛋白质，DNA，药物，而不会影响分辨率。尽管诺丁汉大学（UoN）拥有一系列显微镜设备，但在分辨率方面存在明显的差距，这需要SRM提供的尖端技术来将研究带入诺丁汉生命科学目前无法实现的领域。其中一些领域包括：(i)微生物学：更好地了解细菌细胞如何相互作用，以及它们如何在被称为生物膜的细菌群落的细胞内和细胞之间传递分子和信号；生物能：了解一些细菌细胞能量储存库如何转化为生物燃料，从而能够优化这些过程；合成生物学：了解如何开发人造细胞和专门的DNA结构，因为这在不同的工业环境中可能产生重大影响；（iv）干细胞生物学和组织工程：SRM将对理解干细胞特化细胞的发展和组织支架的发展产生重大影响，这将对修复不同受损人体组织所需的再生医学至关重要；植物科学：了解影响作物生产和可持续农业的根发育中的一些信号过程和花粉发育机制；（六）粮食安全：阐明造成农业重大损失的病原体与农场动物宿主细胞之间相互作用的基本机制，最终目标是针对其中一些机制，减少它们对经济的负面影响；（七）分子药理学：促进对药物-目标相互作用的了解，使其得到优化，从而改善健康。因此，获得SRM设施将使联合国能够处理上述领域的关键生物学问题，这些问题将对科学、经济和社会产生重大影响。

For many years there has been a gap in the resolution of Confocal Laser Scanning Microsopy and even with perfect lenses, optimal alignment, and large numerical apertures the optical resolution of this form of light microscopy has been limited to approximately half of the wavelength of the light used meaning that only cellular structures and objects at least 200 to 350 nm apart could be resolved as distinct separate structures. However, much of the fundamental biology of the cell, occurs at the level of micro-molecular complexes in the size range of tens to few hundred nm, i.e., beyond the reach of conventional light microscopy. Super resolution microscopes (SRM) have been developed to break or bypass the classical diffraction limits and shift the optical resolution down to macro-molecular or even molecular levels. It can locate single molecules down to 20nm precision. SRM can also provide particle tracking to follow single molecules, e.g. proteins, DNA, drugs, in a sample without compromising resolution. Although the University of Nottingham (UoN) houses a range of microscopy facilities there is a clear gap in resolution that requires the cutting edge technology SRM provides to take the research into areas that are not currently achievable in Nottingham Life Sciences at present. Some of these areas include: (i) Microbiology: to understand better how bacterial cells interact with each other and how they can transfer molecules and signals within and between cells in bacterial communities known as biofilms; (ii) Bioenergy: to understand how some bacterial cellular energy reservoirs are transformed into biofuels and hence be able to optimize of these processes; (iii) Synthetic Biology: to understand how artificial cells and specialized DNA structures are developed as this can have a significant impact within different industrial contexts; (iv) Stem cell biology and tissue engineering: the SRM will have a significant impact on understanding the development of specialized cells from stem cells and the development of tissue scaffolds which will be paramount in regenerative medicine required for the repair of different damaged human tissues; (v) Plant sciences: to understand some of the signaling processes in root development and the mechanisms of pollen development which impact on crop production and sustainable agriculture; (vi) Food security: to unravel essential mechanisms of interaction between pathogens and host cells of farm animals which are responsible for significant loses in the farm industry with the ultimate aim of targeting some of these to reduce the negative economic impact they have and (vii) Molecular pharmacology: to facilitate the understanding of drug-target interactions enabling their optimization with the consequent improvements to health.Hence the acquisition of a SRM facility will enable UoN to address key biological questions in the above areas which will have a significant impact on science, the economy and society.