Flourescent Probes & Imaging - Networks & Pathways(RMI)

描述(申请人提供)：我们建议建立一个全国可见和响应的中心，专注于荧光探针和成像技术，用于实时和高分辨率地研究活细胞中的途径和网络。拟建的中心将结合匹兹堡现有的两个中心的经验和基础设施组成。该中心的研究部分将创建一个强大的细胞内荧光标记和生物传感器工具箱，可用于研究活细胞途径和网络中的许多蛋白质。强荧光探针开发计划融合了遗传学、蛋白质结构、核酸结构和荧光染料化学。我们计划产生的探针将是基因可表达的，这样外源大分子就不必被运送到活细胞中进行研究。除了技术开发核心项目外，四个出色的“驾驶生物学项目”将成为整个中心计划的一部分。这些项目分别位于匹兹堡大学、卡内基梅隆大学、斯坦福大学和伯克利大学。他们的责任是协助新中心确定最适合发展的技术，并就这些技术的效用提供重要的反馈。成像和信息学技术与新的荧光探针技术相结合，因此这些组合工具将帮助细胞生物学家获得有关活细胞中途径的大量空间和时间信息。该提案包括使荧光探针和成像技术变得强大的计划，以便它们可以在学术研究、药物开发和生物技术方面提供给广泛的细胞生物学家，并传播这些技术和提供培训。

DESCRIPTION (provided by applicant): We propose to form a nationally visible and responsive center focused on fluorescent probe and imaging technologies for investigating pathways and networks in real time and at high resolution in living cells. The proposed Center will be formed by combining the experience and infrastructure of two already existing Centers in Pittsburgh. The research component of the Center will create a powerful toolbox of intracellular fluorescent labels and biosensors that can be used to study many, if not all, the proteins in pathways and networks of living cells. The strong fluorescent probe development program blends genetics, protein structure, nucleic acid structure and fluorescent dye chemistry. The probes we propose to generate will be genetically expressible so that exogenous macromolecules will not have to be transported into the living cells to be studied. Four superb "Driving Biology Projects" are to be part of the overall Center program in addition to the Technology Development Core. These projects are located at the University of Pittsburgh, Carnegie Mellon, Stanford and Berkeley. Their responsibility is to assist the new center in identifying the optimal technologies for development and for providing crucial feedback regarding the utility of the technologies. Imaging and informatics technologies are integrated with the new fluorescent probe technologies so that these combined tools will help cell biologists obtain large amounts of spatial and temporal information about pathways in living cells. Included in the proposal are programs for making the fluorescent probe and imaging technologies robust so that they can be provided to a wide range of cell biologists in academic research, pharmaceutical drug discovery, and biotechnology and to disseminate these technologies and provide training.