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.

在每个人类细胞中有大约23,500个基因。虽然这看起来是一个很大的数字，但事实并非如此 估计在任何时刻细胞内都有超过500,000种蛋白质存在，而且80% 它们存在于蛋白质杂化复合体中。许多蛋白质都是通过翻译后修饰来改变的 影响亚细胞定位、蛋白质活性、蛋白质结合伙伴和细胞器运输。所有这一切 复杂性影响基因表达和细胞功能。重要的是，许多蛋白质的相互作用产生于细胞与细胞之间- 以一种组织受限的方式介导信号传递，我们现在了解到蛋白质-蛋白质相互作用， 信号转导和基因表达是特定于上下文的。例如，一个 给定的在发育过程中表达的基因可能会有很大的不同，当相同的基因在 成体，如在癌细胞中重新表达的胚胎基因(1)。事实上，它可以用下面的话来表述 早期癌细胞内的细胞自主基因改变与改变协同的置信度 在微环境中促进了肿瘤的进展。微环境和语境的重要性 在肿瘤进展中被广泛接受(2)。因此，越来越多的人需要研究遗传和 癌症的分子基础要迁移到整个生物体才能正确捕获相关分子 在适当的背景下的机制。这是分子成像的基本原理，如 华盛顿大学活体细胞和分子成像中心(吴ICMIC)。 特别是，将基因编码的成像记者整合到活细胞和小动物中 癌症模型提供了强大的工具来监测癌症相关的分子、生化和 体内的细胞通路(3-6)。新的动物模型与成像技术相结合(核、磁共振、 宏观和微观尺度上的荧光和生物发光)将使得有可能 实时探索肿瘤细胞与体内微环境相互作用的后果。 突破性的研究表明，分子成像是一种强大的工具，可以使 基因表达、生化反应、信号转导和调控通路的整体可视化 活体内的有机体。正在开发的针对关键活动的新型注射制剂有朝一日可能会 研究人员和临床医生对患者的这些过程进行可视化。随着合适的探头的发展 和用于活体功能成像的仪器，我们识别和测量生物过程的能力 实时技术已经逐渐扩展到整个生物体，从老鼠到人类。