SCANNING/TRANSMISSION MICROSCOPE FOR MULTI-USER FACILITY

本申请寻求资金购买扫描传输 电子显微镜用于高分辨率形态学研究 各种生物样本 我们将为显微镜配备 X射线分析装置和高增益电视摄像机， 生物学元素的测量和高分辨率定位 感兴趣和低辐射剂量成像。 无类似工具 目前，生物医学研究人员可以在 康涅狄格大学斯托尔斯校区。 显微镜将是 安装在一个成熟的多用户设施，并配备经验丰富的工作人员 大学保证会继续提供支持。 PHS支持 项目的主要用户，这将占75%以上的使用， 新仪器，包括研究：1）在纹状体中钙调节 肌肉. 所要求的仪器将用于电子探针x射线 冷冻断裂复制品的微观分析和高分辨率成像， 快速冷冻骨骼的水合和冷冻干燥冷冻切片， 心肌（Cantino）。 2)细胞代谢和结构的变化 在对乙酰氨基酚中毒和恢复期间。 所要求的文书将 用于肝，肾， 和其他器官（Cohan和Khairallah）。 3)识别和 生长导向因子和粘附因子的定位 周围神经和靶组织联合的形成。 的 要求的仪器将用于超微结构和免疫化学 问题研究 还将进行分析研究，作为 这两名（独立）调查员（Covault， Landmesser）。 4)Ca++通道发育的调控及调控 轴突的存活。 新仪器将用于 用于免疫化学和超微结构研究（皮拉尔）。 5)热效应 休克对肾脏极化单层结构和功能的影响 上皮细胞 新仪器将用于关联超微结构 生理状态。 使用分析方法定位P和Ca 系统将代表一个新的方向（Renfro）。 6)质膜 功能使用磷脂酶探针。 将使用所要求的仪器 用于超微结构分析，以监测制剂中的膜结构 用于生化分析。 囊泡的进一步表征， 将增加分析显微镜检查（Rosenberg）。 7)初步步骤 烟草花叶病毒的形态发生 新的显微镜将提供 研究高辐射敏感性冷冻核材料所需的能力 低电子剂量下的水合样品（Schuster和Raghavendra）。

This application seeks funding for the purchase of a scanning transmission electron microscope to be used for high-resolution morphological studies of diverse samples of biological interest. We will equip the microscope with an x-ray analysis device and a high-gain TV camera for quantitative measurement and high-resolution localization of elements of biological interest and low-irradiation dose imaging. No instrument with similar capabilities currently is available to the biomedical researchers at the Storrs campus of the University of Connecticut. The microscope will be installed in an established multi-user facility with an experienced staff and its continued support is assured by the University. PHS-supported projects of major users, which will account for more than 75% of the use of the new instrument, include studies of: 1) Ca regulation in striated muscle. The requested instrument will be used for electron probe x-ray microanalysis and high-resolution imaging of freeze-fracture replicas and hydrated and freeze-dried cryosections of rapidly frozen skeletal and cardiac muscle (Cantino). 2) Changes in cellular metabolism and structure during acetaminophen toxicity and recovery. The requested instrument will be used for ultrastructural and immunochemical studies in liver, kidney, and other organs (Cohan and Khairallah). 3) Identification and localization of growth guidance and adhesion factors in the outgrowth of peripheral nerves and formation of target tissue associations. The requested instrument will be used for ultrastructural and immunochemical studies. Analytical studies would also be undertaken as a new direction of investigation by these two (independent) investigators (Covault, Landmesser). 4) Regulation of development of Ca++ channels and regulation of axonal survival during development. The new instrument would be used for immunochemical and ultrastructural studies (Pilar). 5) Effects of heat shock on the structure and function of polarized monolayers of kidney epithelia. The new instrument would be used to correlate ultrastructure with physiological status. Localization of P and Ca using the analytical system will represent a new direction (Renfro). 6) Plasma membrane function using phospholipase probes. The requested instrument will be used for ultrastructural analysis to monitor membrane structure in preparations used for biochemical analysis. Further characterization of vesicles by analytical microscopy will be added (Rosenberg). 7) Initial steps in the morphogenesis of tobacco mosaic virus. The new microscope will provide capabilities necessary for studies of highly radiation-sensitive frozen hydrated samples at low electron dose (Schuster and Raghavendra).