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Fluorescent Biosensors for Networks and Pathways

用于网络和通路的荧光生物传感器

基本信息

批准号：
8536340
负责人：
Alan S. Waggoner
金额：
$ 311.53万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8536340
关键词：
Acetylesterase Amino Acid Sequence Automobile Driving Beds Binding Biochemistry Biological Biology Biomedical Research Biosensor Cataloging Catalogs Cells Cellular biology Chemistry Communities Computer software Data Detection Development Diagnosis Diffuse Discipline DsRed Dyes Energy Transfer Engineering Enzyme Kinetics Fluorescence Fluorescence Resonance Energy Transfer Fluorescent Dyes Fluorescent Probes Funding GTP-Binding Proteins Gene Expression Genetic Genetic Engineering Genome Guanosine Triphosphate Phosphohydrolases Image Individual Industry Informatics Instruction Integrins Kinetics Knowledge Label Laboratories Lead Life Location Maps Membrane Potentials Methods Mission Modeling Molecular Molecular Biology Nobel Prize Oxidation-Reduction Pathway interactions Phosphoric Monoester Hydrolases Phosphotransferases Physiological Positioning Attribute Post-Translational Protein Processing Process Program Development Protein translocation Proteins Regulation Relative (related person)Reporter Research Research Infrastructure Research Personnel Resolution Resources Roentgen Rays Role Site Structure Technology Technology Transfer Testing Time Training and Infrastructure Universities catalyst cytokine drug discovery enzyme activity experience fluorophore frontier genetic regulatory protein high throughput screening human disease interest macromolecule molecular dynamics novel novel strategies outreach programs protein degradation protein expression protein protein interaction sensor small molecule structural biology technology development tool

项目摘要

PROJECT SUMMARY (See Instructions): We propose to continue a nationally visible and responsive center focused on the development of novel fluorescent biosensor and detection technologies for investigating pathways and networks in real time and high spatial resolution in living cells. The renewed center retains the combined experience and infrastructure of two existing centers in Pittsburgh: the Molecular Biosensors and Imaging Center at Carnegie Mellon University and the Center for Biologic Imaging at the University of Pittsburgh. The Technology Development (Core 1) component of the center will create a powerful toolbox of intracellular fluorescent biosensors and reporters that can be used to study many, if not all, of the pathway proteins and activities in living cells. This fluorescent biosensor development program integrates efforts across multiple disciplines, including dye chemistry, molecular biology, biochemistry, structural biology, modeling, cell biology, image acquisition and analysis, and high throughput screening. We have made substantial progress in this effort during the previous 3 years of funding. Four exciting Driving Biology Projects (Core 2) are essential to the technology development effort in Core 1. These DBPs are focused on important and currently un-addressable biological problems, and will serve both as test-beds for the technology and compelling demonstrations of the value of the biosensors and reporters developed in this program. The Infrastructure (Core 3) is provided through the Center for Biologic Imaging at the University of Pittsburgh. The role of the CBI is to act as the application and outreach ami of the project as a whole by testing the new biosensors with challenging biological problems. During the last cycle of this proposal the clear mission of the CBI evolved to become the catalyst in probe implementation, and to strengthen and broaden the impact of the new probes developed by MBIC. This is achieved by providing facilities and expertise to test and validate the probes in the context of the driving biological projects, and ultimately, the biomedical research community at large. The program contains a significant technology transfer component to disseminate concepts, knowledge, software, materials, and resources to users in both academic research labs and industry. This is achieved in our Infrastructure, Training, and Dissemination cores (Core 3,4, 5) and through the technology transfer activities in the Management core (Core 6).

项目摘要（参见说明）：我们建议继续建立一个全国可见且响应迅速的中心，专注于开发新型荧光生物传感器和检测技术，以实时和高空间分辨率研究活细胞中的通路和网络。更新后的中心保留了匹兹堡两个现有中心的综合经验和基础设施：卡内基梅隆大学分子生物传感器和成像中心大学和匹兹堡大学生物成像中心。该中心的技术开发（核心 1）部分将创建一个强大的细胞内荧光生物传感器和报告工具箱，可用于研究活细胞中的许多（如果不是全部）途径蛋白质和活动。该荧光生物传感器开发计划整合了多个学科的努力，包括染料化学、分子生物学、生物化学、结构生物学、建模、细胞生物学、图像采集和分析以及高通量筛选。在过去三年的资助中，我们在这方面取得了实质性进展。四个激动人心的驱动生物学项目（核心 2）对于核心 1 的技术开发工作至关重要。这些 DBP 专注于重要且目前无法解决的生物问题，并将作为该技术的测试平台，并引人注目地展示该计划中开发的生物传感器和报告器的价值。基础设施（核心 3）由匹兹堡大学生物成像中心提供。 CBI 的作用是通过测试具有挑战性的生物问题的新型生物传感器，充当整个项目的应用和推广代表。在该提案的最后一个周期中，CBI 的明确使命演变为成为探针实施的催化剂，并加强和扩大 MBIC 开发的新探针的影响。这是通过提供设施和在推动生物项目并最终在整个生物医学研究界的背景下测试和验证探针的专业知识。该计划包含重要的技术转让部分，旨在向学术研究实验室和工业界的用户传播概念、知识、软件、材料和资源。这是通过我们的基础设施、培训和传播核心（核心 3,4,5）以及通过技术转让实现的管理核心（核心 6）的活动。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Malachite green mediates homodimerization of antibody VL domains to form a fluorescent ternary complex with singular symmetric interfaces.

DOI：
10.1016/j.jmb.2013.08.014
发表时间：
2013-11-15
期刊：
JOURNAL OF MOLECULAR BIOLOGY
影响因子：
5.6
作者：
Szent-Gyorgyi, Chris;Stanfield, Robyn L.;Andreko, Susan;Dempsey, Alison;Ahmed, Mushtaq;Capek, Sarah;Waggoner, Alan S.;Wilson, Ian A.;Bruchez, Marcel P.
通讯作者：
Bruchez, Marcel P.

Reply to 'Complexity of molecular crowding in cell-free enzymatic reaction networks'.

回复“无细胞酶反应网络中分子拥挤的复杂性”。

DOI：
10.1038/nnano.2014.111
发表时间：
2014
期刊：
Nature nanotechnology
影响因子：
38.3
作者：
Tan,Cheemeng;Saurabh,Saumya;Bruchez,MarcelP;Schwartz,Russell;LeDuc,Philip
通讯作者：
LeDuc,Philip

Immuno-proteomics: Development of a novel reagent for separating antibodies from their target proteins.

免疫蛋白质组学：开发一种用于将抗体与其靶蛋白分离的新型试剂。

DOI：
10.1016/j.bbapap.2014.10.011
发表时间：
2015
期刊：
Biochimica et biophysica acta
影响因子：
0
作者：
Ganesan,Vinitha;Schmidt,Brigitte;Avula,Raghunandan;Cooke,Dagney;Maggiacomo,Taylor;Tellin,Lawton;Ascherman,DanaP;Bruchez,MarcelP;Minden,Jonathan
通讯作者：
Minden,Jonathan

Genetically targeted fluorogenic macromolecules for subcellular imaging and cellular perturbation.