ImageXpress Micro Cellular Imagining and Analysis System

描述(由申请人提供)：本提案的目标是请求一个高通量成像和分析系统，以支持科罗拉多大学博尔德分校(CU-Boulder)研究人员在基于成像的研究中的创新研究。该系统是一个完全集成的硬件和软件系统，用于采集和分析固定细胞和活细胞的高通量屏幕图像。该系统包括使用激光和基于图像的自动聚焦技术的自动图像采集和集成的数据存储和分析软件，该软件包括各种图像处理模块，使该系统能够用于广泛的基于图像的生物分析。它还集成了实时活细胞成像研究所需的环境控制和液体处理模块。成功收购这一最先进的成像和分析系统将促进NIH资助的研究人员在许多学科中的许多合作。四个研究项目利用RNAi筛选在转化生长因子-β信号转导、细胞极性复合体形成、线粒体金属动态平衡和p53凋亡反应中的新蛋白质；五个项目筛选新的小分子生物探针，如E3泛素连接酶抑制剂、组蛋白赖氨酸去甲基酶调节剂和细菌发病机制抑制剂；三个研究项目侧重于实时活细胞成像研究，包括W-RAMP复合体形成、转化生长因子-β诱导的Smad转位、通过神经元到胶质细胞的信号转导促进疼痛、探索胶质细胞调节临床相关阿片类药物作用的潜力以及高迁移率族蛋白Box 1蛋白在中枢神经系统现象中的作用。这些研究项目的成功实施将导致发现新的治疗靶点和临床开发的先导化合物。除了促进拟议的研究项目外，我们还期待该系统为将高通量基于图像的屏幕和实时活细胞成像研究的尖端能力扩展到更大的研究社区提供有用的经验基础。最后，建议的仪器和数据集将通过仪器实验室课程、化学生物学/药物发现研究生课程和生物物理学课程，通过本科生研究项目提供给高水平的研究生和本科生研究项目。 公共卫生相关性：所要求的最先进的成像和分析系统将促进NIH资助的一些研究项目，如细菌发病机制、肿瘤抑制因子p53信号转导和疼痛促进。这些研究项目的成功实施将导致发现新的治疗靶点和临床开发的先导化合物。

DESCRIPTION (provided by applicant): The goal of this proposal is to request a high-throughput imaging and analysis system to support innovative research in imaged-based research for investigators at the University of Colorado, Boulder (CU-Boulder). This system is a fully integrated hardware and software system for acquisition and analysis of images for high-throughput screens of both fixed and live cells. The system includes an automated image acquisition using both laser- and image-based autofocus technology and an integrated data storage and analysis software including a variety of image processing modules, which enables this system to be used in a wide range of image-based biological assays. It also incorporates environmental control and liquid handling modules that are required for real-time live-cell imaging studies. The successful acquisition of this state-of-the-art imaging and analysis system will promote a number of collaborations between NIH- funded investigators in many disciplines. Four research projects screen for novel proteins in TGF-beta signaling, cell polarity complex formation, mitochondria metal homeostasis and p53 apoptotic responses using RNAi screen; five projects screen for novel small-molecule bioprobes, such as E3 ubiquitin ligase inhibitors, histone lysine demethylase modulators, and inhibitors of bacterial pathogenesis; three research projects focus on the real-time live-cell imaging studies including W-RAMP complex formation, TGF-beta induced Smad translocation, pain facilitation via neuron-to-glia signaling, exploring the potential of glia for regulating clinically relevant opioid actions, and role of high mobility group box 1 protein in central nervous system phenomena. Successful execution of these research projects will lead to discovery of novel therapeutic targets and lead compounds for clinical development. In addition to facilitate the proposed research projects, we also expect this system to provide a useful experience base for extending cutting-edge capabilities in high-throughput image-based screen and real-time live-cell imaging studies to the larger research community. Finally, the proposed instrument and datasets will be available for upper level graduate and undergraduate research projects through undergraduate research projects through instrument laboratory courses, a graduate chemical biology/drug discovery course, and a biophysics course. PUBLIC HEALTH RELEVANCE: The requested state-of-the-art imaging and analysis system will facilitate a number of NIH-funded research projects, such as bacterial pathogenesis, tumor suppressor p53 signaling, and pain facilitation. Successful execution of these research projects will lead to discovery of novel therapeutic targets and lead compounds for clinical development.