Abberior 3D-STED microscope for super-resolution imaging

项目总结 我们正在申请资金，以购买Abberior Instruments设备线3D STED显微镜，以 在布兰代斯大学共焦成像核心设施维护。这台显微镜将为主要用户服务 由10名NIH资助的研究人员和两名将申请NIH资助的初级教职员工组成的小组，我们 欢迎更多来自Brandeis和该地区生物医学科学的用户。我们的团体追求广泛的 各种与人类健康有关的项目，包括衰老、癌症生物学、神经退行性变、癫痫、 学习和记忆，以及多细胞生物体的起源。这些不同研究的一个共同特点是 对光学显微镜的高度依赖和对了解分子尺度如何 结构(几十纳米大小)控制细胞和组织规模的生物过程。我们的一个主要障碍是 这些领域的进展是我们机构缺乏能够解析这些微小结构的成像系统 感兴趣的人。在克服此分辨率障碍的众多策略中(如STORM、SOFI和 扩展显微镜)，STED显微镜是我们研究界的理想解决方案：它从根本上 共焦显微镜，我们的用户群在共焦的各个方面都拥有异常广泛和深厚的专业知识 显微镜包括样品制备、成像和严格的定量图像分析。一个STED 显微镜将代表着分辨率比我们目前的能力提高五倍，并将打开 沿着我们现在完全看不见的生物学之路前进。在仪器上收集的数据将有助于回答 许多悬而未决的问题：新型治疗纳米粒如何靶向亚细胞细胞器来抗击癌症？多么 神经元突触的信号发送和接收结构是否组装在一起来控制学习和 记忆还是预防癫痫？对衰老和神经退行性变重要的分子如何定位和发挥作用 在这些突触上？由于这些结构中的每一个都很小，我们无法回答这些问题 以我们目前的技术。除了分辨率的提高，这个系统还配备了一些功能 这有助于深度体积成像和实时成像，这将使我们能够在体内进行实验 活组织。总之，Abberior STED系统将极大地提高我们发现 纳米级分子和细胞结构控制着细胞和组织生物学，这与人类健康和 疾病。

PROJECT SUMMARY We are requesting funds to purchase an Abberior Instruments FACILITY line 3D STED microscope to be maintained in the Brandeis University Confocal Imaging Core Facility. This microscope will serve a primary user group of 10 NIH funded investigators, and two junior faculty who will be applying for NIH funding, and we welcome additional users from the biomedical sciences at Brandeis and the region. Our groups pursue a wide variety of projects relevant to human health including aging, cancer biology, neurodegeneration, epilepsy, learning and memory, and the origins of multicellular organisms. A common feature of these diverse studies is a deep reliance on optical microscopy and an overarching interest in understanding how molecular-scale structures (tens of nanometers in size) control cell and tissue-scale biological processes. A major barrier to our progress in these areas is the lack of an imaging system at our institution that can resolve these tiny structures of interest. Among the many strategies to overcome this resolution barrier (such as STORM, SOFI, and expansion microscopy), a STED microscope is the ideal solution for our research community: It is fundamentally a confocal microscope, and our user base has exceptionally broad and deep expertise in all aspects of confocal microscopy including sample preparation, imaging, and rigorous quantitative image analysis. A STED microscope would represent a five-fold improvement in resolution over our current capabilities and would open up avenues of biology that are completely invisible to us now. Data collected on the instrument will help answer many open questions: How do novel therapeutic nanoparticles target subcellular organelles to fight cancer? How do signal sending and receiving structures at neuronal synapses assemble together to control learning and memory or prevent epilepsy? How do molecules important to aging and neurodegeneration localize and function at these synapses? Because of the small size of each of these structures, these are questions we cannot answer with our current technology. Beyond the increase in resolution this system provides, it is equipped with features that facilitate deep volumetric imaging and live imaging, which will allow us to perform experiments in vivo in living tissues. Together, the Abberior STED system would profoundly improve our ability to discover how nanoscale molecular and cellular structures control cell and tissue biology that is relevant to human health and disease.