Alliance for Cellular Signaling

细胞信号联盟

• 批准号: 6961953
• 负责人: ALFRED G GILMAN
• 金额: $ 616.44万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6961953
• 关键词: biological signal transduction; cell biology; cell cell interaction; cell cycle proteins; cell line; cooperative study; cytology; fluorescence resonance energy transfer; fluorescent dye /probe; high throughput technology; information dissemination; molecular biology information system; single cell analysis

DESCRIPTION (provided by the applicant): We hold these truths to be self-evident: 1) Cellular signaling mechanisms are vitally important regulators of virtually all cellular functions; understanding them in depth is thus a critical aspect of both basic and applied biology and medicine. 2) Biological systems of such importance are spectacularly complex. The complexity of signaling networks is characterized by simultaneous use of multiple distinct biochemical mechanisms, related members of multi- gene families, and splice products of single genes. This apparent redundancy permits a) partitioning of signaling events to distinct subcellular locations, b).distinct controls for inputs that lead to the same endpoint, c) controlled additivity or non-additivity of parallel or similar pathways, d) variably non-linear response functions, e) robustness to disruption by into untoward inputs, f) distinct patterns of response kinetics and/or amplitude, and g) the ability to developmentally or adaptively alter individual ligand-response relationships differentially. And importantly: 3) human minds are incapable of understanding the emergent properties of such systems by inspection of even the most accurately annotated maps of the circuitry. Quantitative models will be necessary, and the development of such models at both the cellular and organismal level will be a legacy of 21st century biomedical science. Our progress to date points to signaling systems built from modules with measurable degrees of interactions between modules. We are well-positioned to further our knowledge by application and development of a) tools for measuring the "state" of module, components, b) tools for measuring information flow between components and modules, c) a program underway to collect data and model quantitatively specific modules operating in a limited time frame (the FXM project), and d) approaches for developing and testing quantitative models of more complex processes operating over longer times (e.g., cytokine secretion). We believe the AfCS is both a scientific and a social success. Our website serves the scientific community as an invaluable source of experimental data that are accessible to and being actively mined by non-AfCS investigators, signaling information (in a database that includes nearly 4000 molecules), useful reagents (including thousands of DNA constructs), lab protocols, and more. These AfCS efforts are being conducted on a scale unprecedented in previous work with vertebrate cells. In the aggregate, these accomplishments reflect success of an initially risky social experiment the attempt to create a transcontinental consortium of biological laboratories collaborating effectively to achieve a common goal. The potentially unwieldy consortium has revealed a surprising capacity to meet difficult challenges.

描述（由申请人提供）：我们认为这些真理是不言而喻的：1）细胞信号传导机制几乎是所有细胞功能的重要调节剂；因此，深入了解它们是基础生物学和医学的关键方面。 2）如此重要的生物系统非常复杂。信号网络的复杂性的特征在于同时使用多种不同的生化机制，多基因家族的相关成员以及单基因的剪接产物。 This apparent redundancy permits a) partitioning of signaling events to distinct subcellular locations, b).distinct controls for inputs that lead to the same endpoint, c) controlled additivity or non-additivity of parallel or similar pathways, d) variably non-linear response functions, e) robustness to disruption by into untoward inputs, f) distinct patterns of response kinetics and/or amplitude, g）能够在发育或适应性地改变单个配体反应关系的能力差异化。重要的是：3）人类的思想无法通过检查电路的最精确注释的地图来理解此类系统的新兴特性。定量模型将是必要的，并且在细胞和生物水平上的此类模型的发展将是21世纪生物医学科学的遗产。 我们的进度到日期指向由模块之间的模块构建的信号系统。 We are well-positioned to further our knowledge by application and development of a) tools for measuring the "state" of module, components, b) tools for measuring information flow between components and modules, c) a program underway to collect data and model quantitatively specific modules operating in a limited time frame (the FXM project), and d) approaches for developing and testing quantitative models of more complex processes operating over longer times (e.g., cytokine secretion). 我们认为AFCS既是科学的，又是社会成功。我们的网站将科学界作为实验数据的宝贵来源，可供非AFC研究人员访问和积极开采，信号信息（在包含近4000个分子的数据库中），有用的试剂（包括数千种DNA构建体），实验室协议等。这些AFC的努力是在先前与脊椎动物细胞的工作中以前所未有的规模进行的。在总体上，这些成就反映了最初有风险的社会实验的成功，试图创建一个有效合作以实现共同目标的生物实验室的跨大陆财团。潜在的笨拙的财团揭示了应对困难挑战的惊人能力。