Administrative Core

每个人类细胞中大约有23，500个基因。虽然这似乎是一个很大的数字，但它是 据估计，在任何一个时刻，细胞内都存在超过50万种蛋白质，而且，80%的蛋白质都存在于细胞内。 这些存在于蛋白质杂合物中。许多蛋白质通过翻译后修饰而改变， 影响亚细胞位置、蛋白质活性、蛋白质结合伴侣和细胞器运输。这一切 复杂性影响基因表达和细胞功能。重要的是，许多蛋白质相互作用产生于细胞与细胞之间， 以组织限制的方式介导信号传导，我们现在知道蛋白质-蛋白质相互作用， 信号传导和基因表达具有环境特异性。例如， 在发育过程中表达的给定基因可能是完全不同的，当相同的基因在发育过程中表达时， 成人，如在癌细胞中重新表达的胚胎基因所见（1）。事实上，可以说， 相信在早期癌细胞内的细胞自主遗传变化与改变合作 在微环境中会导致肿瘤进展。微环境和背景的重要性 在肿瘤进展中是公认的（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 在适当的背景下。这构成了如本发明所设想的分子成像的基本原理的基础。 华盛顿大学体内细胞和分子成像中心（WU ICMIC）。 特别地，将遗传编码的成像报告子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，生物化学， 体内的细胞途径（3 - 6）。新的动物模型结合成像技术（核，MR， 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， 基因表达、生化反应、信号转导和调控通路的整体可视化 体内的有机体。正在开发的针对关键活动的新型注射剂可能有一天能够 研究人员和临床医生可视化这些过程中的病人。随着合适探针的发展 和仪器的功能成像在体内，我们的能力，以确定和测量生物过程中， 实时已经逐渐扩展到整个生物体，从小鼠到人类。

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.