FLUORESCENT PROBES & IMAGING FOR NETWORKS & PATHWAY(RMI)

描述（由申请人提供）：我们建议建立一个全国性的可见和响应中心，专注于荧光探针和成像技术，以实时和高分辨率地研究活细胞中的通路和网络。拟建的中心将结合匹兹堡两个现有中心的经验和基础设施。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，可用于研究许多（如果不是全部的话）活细胞通路和网络中的蛋白质。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。我们建议产生的探针将是遗传可表达的，因此外源性大分子将不必被运送到活细胞进行研究。除了技术开发核心外，四个卓越的“驱动生物学项目”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。它们的责任是协助新中心确定促进发展的最佳技术，并就这些技术的用途提供关键的反馈。成像和信息学技术与新的荧光探针技术相结合，使这些组合工具将帮助细胞生物学家获得关于活细胞通路的大量空间和时间信息。提案中包括使荧光探针和成像技术更加强大的计划，以便它们可以提供给广泛的细胞生物学家进行学术研究，药物发现和生物技术，并传播这些技术并提供培训。

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.