PURCHASE OF AN ELECTRON MICROSCOPE AND CCD CAMERA

本申请申请资金用于电子显微镜（EM）和CCD相机直接采集数字图像。目前，EM设施有两台自1979年和1984年以来连续运行的显微镜。由于这两种仪器都代表着过时的技术，而且替换部件变得稀缺或不可用，因此它们目前对Fox Chase癌症中心（FCCC）的研究人员来说显然不是最理想的。美国国立卫生研究院资助的13名FCCC研究人员将是EM的主要用户，他们的研究兴趣差异很大。大多数研究人员使用标准光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来选择的，目的是满足研究人员的即时和长期需求。本应用程序中描述的研究程序旨在了解人类癌症和其他疾病的过程。这将通过超微结构的电镜研究和细胞内定位和运输生物学上重要的分子，包括染色质，对DNA复制、细胞分裂和减数分裂的调节至关重要的结构，致癌基因和肿瘤抑制基因的产物，以及病毒成分来完成。计划的项目包括研究慢性肝炎在肝细胞中向恶性肿瘤的进展以及阐明新发现的肿瘤抑制因子的功能。对逆转录病毒蛋白核输入机制的分析与癌症和艾滋病都有关系。在其他几个项目中对细胞周期和细胞分裂的控制方面的研究将为癌症的基本机制提供相关信息。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FCCC的EM核心设施安装和操作。这个共享设施在中央实验室翼有一个理想的位置，为FCCC的大多数NIH资助的实验室提供服务。训练有素和积极主动的工作人员将协助这一应用的管理和科学组成部分，其方式应理想地适合于共享资源设施。

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 Because both instruments represent outdated technology and replacement parts are becoming scarce or unavailable, their present utility to investigators at Fox Chase Cancer Center (FCCC) is clearly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.