Chemical Probes to Study Metal Biology

研究金属生物学的化学探针

• 批准号: 10374112
• 负责人: Christopher J. Chang
• 金额: $ 38.85万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374112
• 关键词: Animal Model; Animals; Antioxidants; Behavior; Behavioral; Biological; Biological Models; Biology; Bioluminescence; Body part; Brain; Cell Nucleus; Cell model; Cells; Chemicals; Chemistry; Confounding Factors (Epidemiology); Copper; Dependence; Detection; Development; Diabetes Mellitus; Diet; Disease; Environment; Enzymes; Evaluation; Fluorescence; Fluorescence Resonance Energy Transfer; Foundations; Gene Expression Profiling; Generations; Genetic; Glutathione; Goals; Golgi Apparatus; Health; Heart Diseases; Homeostasis; Human; Image; Imaging Device; Iron; Label; Life Style; Malignant Neoplasms; Membrane; Metabolic Diseases; Metals; Mitochondria; Modality; Modeling; Monitor; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurophysiology - biologic function; Neurotransmitters; Noise; Nutrient; Obesity; Optics; Organelles; Organism; Output; Oxidation-Reduction; Oxidative Stress; Pathologic; Pathway interactions; Physiological; Physiological Processes; Play; Property; Proteins; Proteomics; Puromycin; Reagent; Reporter; Research Support; Resolution; Respiration; Role; Sampling; Signal Transduction; Stains; Structure; System; Techniques; Tissues; Transition Elements; Vertebrates; Work; Zebrafish; base; bioluminescence imaging; collaborative environment; design; detection method; fluorescence imaging; healing; imaging modality; in vivo imaging; innovation; knock-down; luciferin; luminescence; neural circuit; next generation; oxidative damage; public health relevance; ratiometric; receptor; relating to nervous system; stress management; tool; trafficking; wound healing

Project Summary/Abstract Copper is an essential metal nutrient that plays important roles in human health and disease. The potent redox activity of copper is required for a diverse array of physiological processes including respiration, antioxidant defense, neurotransmitter synthesis, and wound healing. However, dysregulated copper homeostasis can contribute to metabolic diseases like obesity and diabetes as well as cancer, heart disease, and neurodegenerative disorders, often through aberrant oxidative stress and damage pathways. To help decipher the contributions of copper to healthy and disease states, we are developing new chemical tools to enable copper-specific imaging in living systems across a broad range of biological models, from subcellular compartments to cells to whole animals. The scientific premise is that building a copper imaging toolkit will provide foundational chemical reagents to further our understanding of the roles of copper in both physiological and pathological situations. This competitive renewal application is driven by design innovations where we invent new generalizable, activity-based sensing platforms for copper detection, as well as scientific rigor in the synthesis and use of multiple characterization techniques to apply these tools in cell and animal models. Specifically, we will pursue protein-labeled copper probes to study how copper is stored, trafficked, and utilized at the subcellular level, chemiluminescent indicators to enable dynamic and longitudinal copper imaging at the live animal level, and studies to probe how copper contributes to managing oxidative stress in neuronal cultures and regulating neural circuitry and behavior in zebrafish models.

项目摘要/摘要 铜是一种必需的金属营养素，在人类健康和疾病中起重要作用。有效的氧化还原 铜的活性是多种生理过程所需的，包括呼吸，抗氧化剂 防御，神经递质的合成和伤口愈合。但是，铜稳态失调可以 有助于肥胖和糖尿病等代谢疾病以及癌症，心脏病和 神经退行性疾病通常是通过异常的氧化应激和损伤途径。帮助破译 铜对健康和疾病状态的贡献，我们正在开发新的化学工具以实现 从亚细胞的各种生物模型的生物系统中的铜特异性成像 隔间到整个动物的细胞。科学的前提是，构建铜成像工具包将 提供基础化学试剂，以进一步了解铜在两种生理学中的作用 和病理状况。该竞争性更新应用程序是由设计创新驱动的 发明新的可推广的，基于活动的传感平台，用于铜检测，以及在 合成和使用多种表征技术将这些工具应用于细胞和动物模型。 具体而言，我们将追求蛋白质标记的铜探针来研究铜的存储，贩运和利用方式 在亚细胞水平上，化学发光指标可以在 活动物水平和研究探测铜如何促进神经元中的氧化应激 培养和调节斑马鱼模型中的神经回路和行为。