MRI: Acquisition of Integrated Instrumentation to Facilitate Correlative Light and Electron Microscopy of Cellular Systems

该奖项是为了奖励为建立一个设施所需的仪器设备，该设施将为了解细胞的功能组织提供一个新的窗口。该设施将包含一个用于冷冻准备的综合仪器系统，以促进两个研究领域：1)相关光学和电子显微镜(Clem)，以及2)玻璃体切片的冷冻电子断层扫描。细胞具有复杂的细胞内成分间的相互作用，每个成分都表现出精确的空间定位和时间动力学。荧光显微镜的进步使人们能够精确跟踪单独标记的分子；这可以以高时间分辨率为活细胞的动态细胞过程提供重要的见解。然而，目前的光学显微镜技术缺乏EM的分辨率，无法在高空间分辨率的分子水平上揭示结构细节。EM图像仅提供动态细胞内过程的静态快照。通过该奖项获得的仪器将能够以两种方式结合光和EM的优势：1)通过延时成像跟踪活细胞中单个细胞内结构的动态，随后快速冷冻标本，然后通过EM和三维(3D)重建方法对同一细胞进行分析；2)扫描大片细胞或组织，以确定低频发生的EM分析的特定部位，从而能够对否则不可行的细胞结构进行EM研究。这种相关的方法将为以下方面提供新的见解：1)大分子、细胞和组织的结构和功能；2)调节细胞功能的动态时空细胞内和细胞间相互作用。这一新的设施将培养新一代科学家，他们将应用相关光学和电子显微镜在细胞生物学和神经生物学方面进行创新实验。该设施将在大波士顿地区独一无二，并将促进该大学和该地区其他机构的调查人员之间的互动和合作。该设施将培训本科生、研究生和博士后研究员尖端技术。将开发和实施关于成像技术和应用的新的理论和实践课程；这些新课程将向邻近机构的成员开放。该大学为来自其他校区的少数民族本科生举办暑期研究实习项目。作为研究计划的一部分，该计划的实习生将有权使用这一设施。超过40%的生命科学教师是女性，该奖项由三名女教师带头，为学生提供了优秀的榜样。该设施将整合教育、培训和研究，最终提供对蜂窝架构和功能的新的基本见解。

This award is for the acquisition of instrumentation needed to establish a facility that will provide a new window into the functional organization of cells. The facility will contain an integrated system of instruments for cryo-preparation to facilitate two research areas: 1) correlative light and electron microscopy (CLEM), and 2) cryo-electron tomography of vitreous sections. Cells have complex interactions among intracellular components, each of which exhibits precise spatial localization and temporal dynamics. Advances in fluorescence light microscopy allow precise tracking of individually labeled molecules; this can provide important insights into dynamic cellular processes of living cells with high temporal resolution. However, current light microscope technology lacks the resolution of EM to reveal structural details at a molecular level with high spatial resolution. EM images provide only static snapshots of dynamic intracellular processes. The instrumentation acquired through this award will enable a combination of the advantages of light and EM in two ways: 1) Tracking the dynamics of individual intracellular structures in a living cell by time-lapse imaging, followed by rapid freezing of the specimen and subsequent analysis of the same cell by EM and three-dimensional (3D) reconstruction methods; 2) Scanning large regions of cells or tissues to identify specific sites for EM analysis that occur at low frequency, enabling EM studies of cellular structures that would not otherwise be feasible. This correlative approach will provide new insights into: 1) the structure and function of macromolecules, cells, and tissues, and 2) the dynamic spatiotemporal intra- and intercellular interactions that regulate cellular function.This new facility will train a new generation of scientists who will apply correlative light and electron microscopy to carry out innovative experiments in cell biology and neurobiology. The facility will be unique in the greater Boston area and will facilitate interactions and collaborations among investigators at the university and other institutions in the area. The facility will train undergraduates, graduate students and postdoctoral fellows in cutting-edge technologies. New theoretical and practical courses in imaging techniques and applications will be developed and implemented; these new courses will be open to members of neighboring institutions. The university hosts a summer research internship program for minority undergraduates from other campuses. Interns from this program will have access to this facility as part of their research program. Over 40% of the Life Sciences faculty are female, and this award is spearheaded by three women faculty, providing excellent role models for students. This facility will integrate education, training and research to ultimately provide new fundamental insights into cellular architecture and function.