Abberior 3D-STED microscope for super-resolution imaging

项目摘要 我们正在申请资金购买一台Abberior Instruments FACEBOOK线3D STED显微镜， 在布兰迪斯大学共聚焦成像核心设施中维护。这台显微镜将服务于一个主要用户 一组由10名NIH资助的研究人员和两名将申请NIH资助的初级教师组成，我们 欢迎来自布兰代斯和该地区生物医学科学的其他用户。我们的团体追求广泛的 与人类健康相关的各种项目，包括衰老、癌症生物学、神经退行性疾病、癫痫， 学习和记忆，以及多细胞生物的起源。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，以及对理解分子尺度 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 在这些领域取得的进展是，我们的研究机构缺乏能够分辨这些微小结构的成像系统 感兴趣在克服这一解决障碍的许多策略中（如STORM、SOFI和 扩展显微镜），STED显微镜是我们研究社区的理想解决方案：它从根本上 我们的用户群在共聚焦显微镜的各个方面都有非常广泛和深入的专业知识， 显微镜检查包括样品制备、成像和严格的定量图像分析。的STED 显微镜的分辨率将比我们目前的能力提高五倍， 我们现在完全看不到的生物学途径。仪器上收集的数据将有助于回答 许多悬而未决的问题：新的治疗性纳米颗粒如何靶向亚细胞器来对抗癌症？如何 神经元突触上的信号发送和接收结构是否组装在一起以控制学习， 记忆力好还是预防癫痫？对衰老和神经退化很重要的分子是如何定位和发挥作用的 在这些突触上由于这些结构中的每一个都很小，这些都是我们无法回答的问题 我们现有的技术。除了分辨率的提高，该系统还配备了一些功能， 这有助于深度体积成像和活体成像，这将使我们能够在体内进行实验， 活组织总之，Abberior STED系统将大大提高我们发现如何 纳米级分子和细胞结构控制与人类健康相关的细胞和组织生物学， 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.