Ultramicrotome with necessary accessories

项目摘要/摘要 需要资金购买徕卡Artos超微切割机及其必要的附件，包括 隔振仪表台、钻石刀和玻璃刀制作者。包括在购买遗嘱中 对主要用户和负责监督使用的核心设施工作人员进行培训 乐器。该仪器将安置在校园分子细胞学核心设施(MCC)，在那里它将 更换一台已超过30年、年久失修的超薄切割机。现有的工具不能再被 由于其老化和缺乏更换部件而进行了维修。超微切片对于这项研究是必不可少的 由大型用户组的成员执行。需要此仪器的用户进行的研究包括 遗传性神经变性和视网膜退行性疾病、肌萎缩侧索硬化症的研究 眼科疾病、结缔组织疾病、溶酶体储存疾病和癌症。这台新仪器将 使研究人员能够准备用于光学和电子显微镜(EM)检查的组织切片。 该仪器将使用户能够生产连续截面的色带，可用于产生3- 使用先进的光学显微镜设备对感兴趣的组织和细胞结构进行三维成像 (包括共焦显微镜)大学电子的MCC和电子显微镜能力 显微镜核心设备(EMC)，以获得用于阵列断层扫描的图像。3D图像将使 调查人员解决无法使用显微切开术解决的重要研究问题 该大学目前提供的仪器。例如，似乎视网膜功能受损的患者 正在调查的几种遗传性疾病可能是由于视网膜之间突触的变化 神经元。用透射电子显微镜观察单个薄片很难确定是否是这样 或仅使用共聚焦显微镜进行免疫荧光(IF)。如果用户可以收集连续的部分 包含整个突触结构，并生成可用两种方法检查的3-D复合图像 EM和免疫荧光，使用者将能够可靠地确定是否存在与疾病有关的 突触的结构变化可以解释功能缺陷。众多预期中的项目 用户将受益于具有使用阵列层析进行相关IF和EM的能力。这个 用户将能够使用超微切割机收集的信息将有助于更好地开发 对发病机制的理解和对多种疾病的有效治疗。除了……之外 受益于这项建议中确定的用户的生物医学研究，超微切割机具有 有潜力促进更多潜在生物医学研究人员的研究。许多实验室利用 MCC用于各种显微技术和数字图像处理。通过他们在MCC的工作 设施，他们将意识到超微切片机的可用性和它的能力，并可能选择使用 在他们的研究中。

Project Summary/Abstract Funds are requested to purchase a Leica ARTOS ultramicrotome with necessary accessories including a vibration isolation instrument table, diamond knives, and a glass knifemaker. Included with the purchase will be training for the major users and the core facility staff member responsible for overseeing use of the instrument. The instrument will be housed in the campus Molecular Cytology Core Facility (MCC) where it will replace an ultramicrotome that is over 30 years old and in disrepair. The existing instrument can no longer be serviced due to its age and lack of replacement parts. The ultramicrotome is essential for the research being conducted by members of a large user group. Research by the users that requires this instrument includes studies on hereditary neurodegenerative and retinal degenerative diseases, amyotrophic lateral sclerosis, dry eye diseases, connective tissue disorders, lysosomal storage diseases and cancer. The new instrument will enable the investigators to prepare tissue sections for both light and electron microscopic (EM) examination. The instrument will enable users to produce ribbons of serial sections that can be used to generate 3- dimensional images of tissues and cellular structures of interest using advanced light microscopy equipment (including confocal microscopes) at the MCC and electron microscopy capabilities of the University Electron Microscopy Core Facility (EMC) to obtain images for array tomography. The 3-D images will enable the investigators to address important research questions that cannot be addressed using microtomy instrumentation currently available at the University. For example, it appears that impaired retinal function in several hereditary disorders under investigation may be due to alterations in the synapses between retinal neurons. It is very difficult to determine whether this is the case by examining individual thin sections with TEM or with immunofluorescence (IF) using confocal microscopy alone. If the users can collect serial sections encompassing entire synaptic structures and generate 3-D composite images that can be examined with both EM and immunofluorescence, the users will be able to reliably determine whether there are disease-related structural alterations in the synapses that could explain the functional deficits. Numerous projects of anticipated users would benefit from having the capability of performing correlative IF and EM with array tomography. The information that users will be able to glean using the ultramicrotome will assist in developing better understanding of pathogenesis and in developing effective therapies for numerous disorders. In addition to benefiting the biomedical research of users that are identified in this proposal, the ultramicrotome has the potential to facilitate the research of additional potential biomedical researchers. Many laboratories utilize the MCC for a variety of microscopy techniques and digital image processing. Through their work in the MCC facility, they will become aware of the availability of the ultramicrotome and its capabilities and may elect to use it in their research.