A super-resolution microscope for visualizing cellular structure and dynamics

用于可视化细胞结构和动力学的超分辨率显微镜

• 批准号: RTI-2017-00180
• 负责人: Beh, Christopher
• 金额: $ 10.93万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=616582
• 关键词: super; resolution; microscope; visualizing; cellular

Well below the resolution limit dictated by the wavelength of light, super-resolution confocal microscopes bend the laws of physics to allow cell and developmental biologist to peer down at molecular machines at work within living cells. This Nobel prize winning advance in microscopy is quickly becoming the standard for all high-impact molecular cell biology research, including that conducted by all the member labs of the Centre for Cell Biology, Development and Disease (C2D2) at Simon Fraser University (SFU). In addition to the need for this new super-resolution technology, we are also desperate for another multi-purpose confocal microscope. There currently exists only two confocal microscopes at SFU (for the entire campus) that are generally available to the >183 faculty and student users. Apart from being oversubscribed, these confocal microscopes are aging systems that are reaching the end of their functionality. We propose to acquire a base model super-resolution confocal microscope that offers flexibility to serve both the routine microscopy needs of all SFU researchers but also to provide our institution with its first super-resolution microscope. The TCS SP8 microscope with Hyvolution from Leica can provide tremendous benefits not fulfilled by our current confocal microscopes, namely, a combination of high sensitivity, speed, excellent depth of penetration for any sample, and most importantly, resolving power that is significantly higher. Overwhelming support for the acquisition of this system is underscored by the many pledged contributions, which are needed in addition to the NSERC RTI to purchase the equipment, coming from three SFU Departments (MBB, BISC, BPK), two Faculties (Science, Health Sciences), and a number of individual researchers (the lead applicant Dr. C. Beh and 10 other investigators from across SFU). The added benefit of the proposed system is that it is modular, permitting future upgrades to the base system for even higher resolution capabilities. The flexibility of the proposed microscope system matches the varied NSERC-funded research activities of the molecular cell biology labs at SFU. As the lead applicant, the Beh lab will use the super-resolution microscope to directly visualize the tiny contact sites between internal cellular membranes to understand how these sites mediate the transport of lipids and metabolites back-and-forth. The 10 co-applicants (Drs. T. Beischlag, S. Gorski, N. Harden, N. Hawkins, H. Hutter, M. Moore, G. Rintoul, M. Silverman, G. Tibbits, and D. Vocadlo) will apply the new equipment to various research interests ranging from nerve cell transport and cellular process regulating organ development, to cellular etiologies of cancer and the tracking of intracellular pathogens. As an open resource to all SFU users, trained students will benefit from the mastery of this technologically advanced system for future employment in biotech.

远低于由光波长决定的分辨率极限，超分辨率共聚焦显微镜弯曲物理定律，使细胞和发育生物学家能够向下窥视活细胞内工作的分子机器。这项获得诺贝尔奖的显微镜技术进展正在迅速成为所有高影响力分子细胞生物学研究的标准，包括西蒙弗雷泽大学（SFU）细胞生物学，发育和疾病中心（C2D2）的所有成员实验室进行的研究。除了需要这种新的超分辨率技术，我们还迫切需要另一种多用途共聚焦显微镜。目前只有两个共焦显微镜在SFU（整个校园），一般提供给> 183教师和学生用户。除了被超额认购，这些共焦显微镜是老化的系统，正在达到其功能的终点。 我们建议获得一个基础模型超分辨率共聚焦显微镜，提供灵活性，以满足所有SFU研究人员的常规显微镜需求，同时也为我们的机构提供第一台超分辨率显微镜。徕卡配备Hyvolution的TCS SP8显微镜可以提供我们目前的共聚焦显微镜无法实现的巨大优势，即高灵敏度、速度、对任何样品的出色穿透深度，最重要的是，分辨率显著提高。压倒性的支持，这一系统的收购是强调了许多认捐，这是需要除了NSERC RTI购买设备，来自三个SFU部门（MBB，BISC，BPK），两个院系（科学，健康科学），和一些个人研究人员（主要申请人博士C。Beh和其他10名来自SFU的调查人员）。拟议系统的额外好处是它是模块化的，允许将来升级到基本系统，以获得更高的分辨率能力。 所提出的显微镜系统的灵活性与SFU分子细胞生物学实验室的各种NSERC资助的研究活动相匹配。作为主要申请人，Beh实验室将使用超分辨率显微镜直接观察细胞内膜之间的微小接触部位，以了解这些部位如何介导脂质和代谢物的来回运输。10名共同申请人（T博士）Beischlag，S. Gorski，N. Harden，N.霍金斯，H. Hutter，M.摩尔，G. Rintoul，M. Silverman，G. Tibbits和D. Vocadlo）将把新设备应用于各种研究领域，从神经细胞运输和调节器官发育的细胞过程，到癌症的细胞病因学和细胞内病原体的追踪。作为对所有SFU用户的开放资源，受过培训的学生将受益于掌握这种技术先进的系统，以便将来在生物技术领域就业。