PURCHASE OF AN ELECTRON MICROSCOPE AND CCD CAMERA

该申请要求为电子显微镜（EM）和CCD相机直接获取数字图像提供资金。目前，EM设施有两台显微镜，自1979年和1984年以来一直在连续运行。由于这两种仪器都代表过时的技术，并且更换部件变得稀缺或不可用，因此它们目前对福克斯蔡斯癌症中心（FCCC）的研究人员的效用显然是次优的。13个NIH资助的FCCC研究者的研究兴趣将是EM的主要用户，差异很大。大多数研究人员已经使用标准的光学和荧光显微镜技术进行了初步分析。所要求的设备是根据这些研究兴趣的多样性选择的，目的是满足研究者的短期和长期需求。本申请中描述的研究计划旨在了解人类癌症和其他疾病过程。这将通过对超微结构的EM研究以及生物学重要分子的细胞内定位和运输来实现，这些分子包括染色质、对DNA复制、胞质分裂和减数分裂调节至关重要的结构、癌基因和肿瘤抑制基因的产物以及病毒成分。拟议的项目包括研究慢性肝炎向肝细胞恶性肿瘤的发展，以及阐明最近表征的肿瘤抑制剂的功能。对逆转录病毒蛋白质核输入机制的分析与癌症和艾滋病都有关。在其他几个项目中研究的细胞周期和细胞分裂的控制方面将提供与癌症基本机制相关的信息。所有这些项目都需要EM提供的超微结构分析。所要求的系统将由气候变化框架公约的环境管理核心设施容纳和操作。这个共享设施在中央实验室翼有一个理想的位置，并为大多数国家卫生研究院资助的实验室在FCCC。训练有素和积极主动的工作人员将以最适合共享资源设施的方式协助这一应用的管理和科学部分。

This application requests funding for an electron microscope (EM) and a CCD camera for direct acquisition of digital images. At present the EM Facility has two microscopes which have been running continuously since 1979 and 1984. Because both instruments represent outdated technology and replacement parts are becoming scarce or unavailable, their present utility to investigators at Fox Chase Cancer Center (FCCC) is clearly sub-optimal. The research interests of the 13 NIH funded FCCC investigators who will be the main users of the EM, vary widely. Most of the investigators have carried out preliminary analyses using standard light and fluorescent microscopy techniques. The requested equipment was chosen based upon the diversity of these research interests, with the goal of satisfying the investigators' immediate and long term needs. The research programs described in this application are aimed at understanding human cancer and other disease processes. This will be accomplished through EM studies of ultrastructure and the intracellular localization and trafficking of biologically important molecules including chromatin, structures critical to the regulation of DNA replication, cytokinesis, and meiosis, products of oncogene and tumor suppressor genes, and viral components. Among the proposed projects are study of the progression of chronic hepatitis to malignancy in liver cells and elucidation of the function of recently characterized tumor suppressors. The analysis of the mechanisms of nuclear import of retroviral proteins is pertinent to both cancer and AIDS. Aspects of the control of cell cycle and the cell division studied in several others projects will provide information relevant to basic mechanisms of cancer. All of these projects share a need for ultrastructural analyses provided by EM. The requested system will be housed and operated by the EM Core Facility at FCCC. This shared facility has an ideal location in a central laboratory wing and serves the majority of NIH funded laboratories at FCCC. Highly trained and motivated staff will assist the managerial and scientific components of this application in a manner which should be ideally suited to a shared resource facility.