Administrative Core

行政核心

• 批准号: 8658378
• 负责人: David Piwnica-Worms
• 金额: $ 23.21万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658378
• 关键词: Adult; Animal Cancer Model; Animal Model; Biochemical; Biochemical Reaction; Biological Process; Bioluminescence; Cell physiology; Cells; Collaborations; Development; Embryo; Fluorescence; Functional Imaging; Gene Expression; Genes; Human; Image; Imagery; Imaging Techniques; Injectable; Life; Location; Malignant Neoplasms; Measures; Mediating; Microscopic; Molecular; Molecular Genetics; Monitor; Mus; Mutation; Nuclear; Pathway interactions; Patients; Post-Translational Protein Processing; Process; Protein Binding; Proteins; Regulatory Pathway; Reporter; Research Personnel; Signal Transduction; Time; Tissues; Transduction Gene; Universities; University of Texas M D Anderson Cancer Center; Washington; Whole Organism; base; cancer cell; in vivo; in vivo Cellular and Molecular Imaging Centers; instrumentation; molecular imaging; neoplastic cell; novel; protein protein interaction; tool; trafficking; tumor microenvironment; tumor progression

There are ~23,500 genes in every human cell. While this would appear to be a large number, it is estimated that over 500,000 proteins are present within the cell at any one moment, and furthermore, 80% of these reside in protein heterocomplexes. Many proteins are altered by post-translational modifications that impact subcellullar location, protein activity, protein binding partners and organellar trafficking. All of this complexity impacts gene expression and cell function. Importantly, many protein interactions arise from cell-to-cell- mediated signaling in a tissue-restricted manner and we now understand that protein-protein interactions, signal transduction and gene expression are context-specific. For example, the functional consequences of a given gene expressed during development can be quite different when the same gene is expressed in the adult, as seen with embryonic genes that are re-expressed in cancer cells (1). Indeed, it can be stated with confidence that cell autonomous genetic changes within an incipient cancer cell in collaboration with alterations in the microenvironment contribute to neoplastic progression. The importance of microenvironment and context in neoplastic progression is well accepted (2). Thus, there is increasing need for studies of the genetic and molecular basis of cancer to migrate to the whole organism to correctly capture relevant molecular mechanisms in the proper context. This underlies the rationale for molecular imaging as envisioned by the Washington University In Vivo Cellular and Molecular Imaging Center (WU ICMIC). In particular, integration of genetically encoded imaging reporters into live cells and small animal models of cancer has provided powerful tools to monitor cancer-associated molecular, biochemical, and cellular pathways in vivo (3-6). New animal models combined with imaging techniques (nuclear, MR, fluorescence and bioluminescence) at both macroscopic and microscopic scales will make it possible to explore the consequences of the interactions between tumor cells and microenvironment in vivo in real-time. Ground-breaking studies have demonstrated that molecular imaging is a powerful tool that enables visualization of gene expression, biochemical reactions, signal transduction and regulatory pathways in whole organisms in vivo. Novel injectable agents under development that target key activities may someday enable investigators and clinicians to visualize these processes in patients. With the development of suitable probes and instrumentation for functional imaging in vivo, our ability to identify and measure biological processes in real-time has progressively extended to the whole organism, from mice to humans.

每个人类细胞中都有约23,500个基因。虽然这似乎是一个很大的数字，但 据估计，任何一刻 这些驻留在蛋白质杂膜上。许多蛋白质通过翻译后修饰改变了 影响亚氏菌位置，蛋白质活性，蛋白质结合伴侣和细胞器运输。所有这些 复杂性影响基因表达和细胞功能。重要的是，许多蛋白质相互作用来自细胞到细胞 - 以组织限制的方式介导的信号传导，我们现在知道蛋白质 - 蛋白质相互作用， 信号转导和基因表达是上下文特异性的。例如，一个功能后果 当在发育过程中表达的基因在同一基因中表达时可能完全不同 成人，如在癌细胞中重新表达的胚胎基因所见（1）。确实，可以说 对细胞自主遗传变化的信心与改变 在微环境中，有助于肿瘤进展。微环境和背景的重要性 在肿瘤进展中，人们被广泛接受（2）。因此，越来越需要研究遗传和 癌症的分子基础迁移到整个生物体以正确捕获相关分子 在适当情况下的机制。这是分子成像的基本原理 华盛顿大学体内细胞和分子成像中心（WU ICMIC）。 特别是，遗传编码的成像记者与活细胞和小动物的整合 癌症模型为监测与癌症相关的分子，生化和 体内细胞途径（3-6）。新动物模型与成像技术相结合（核，MR， 在宏观和微观尺度上，荧光和生物发光）将使成为可能 探索实时体内肿瘤细胞与微环境之间相互作用的后果。 开创性的研究表明，分子成像是一种强大的工具，可实现 基因表达，生化反应，信号转导和调节途径的可视化 生物在体内。正在开发的新型注射剂，该针对关键活动可能有一天可以实现 调查人员和临床医生可视化患者的这些过程。随着合适的探针的发展 和用于体内功能成像的仪器，我们识别和测量生物学过程的能力 从老鼠到人类，实时逐渐扩展到整个生物体。