Systems Biology of Cell Decision Processes

生物系统的显著复杂性要求对其进行系统的分析。 该提案的目标是建立一个麻省理工学院单元决策过程卓越中心(CDP) 围绕着一个由细胞生物学家、计算机科学家和微系统工程师组成的跨学科团队 哺乳动物细胞中蛋白质网络和信号转导的系统生物学。的基本假设 CDP中心认为，理解小区决策过程需要开发网络模型 它结合了定量的严谨性和分子的细节。这些模型将是混合模型，包含高度特定的 对关键反应的表示和对系统整体的抽象表示。有效模式 将以严谨和可移植的格式经久不衰，并获取随时间积累的知识。 CDP中心将遵循系统实验和数值计算相结合的研究范式 在操作-测量-挖掘和建模的四步反馈循环中建模。生物学的 该中心的重点将是控制细胞凋亡的信号事件。蛋白质的测定 信号分子的浓度、修饰状态和活性将在多个点上进行 细胞凋亡网络。然后使用几种建模方法对测量结果进行分析 从高度具体到高度抽象。 为了为系统建模收集足够的数据，CDP中心将自动化和标准化 生物化学方法，开发紧凑的基于阵列的分析和设计新的微制造设备 集成的微流控技术和无标签传感器。为了将数据组织和系统化，信息方法将 要开发出支持严格推理方法的。最后，物理化学、结构体系和 将使用贝叶斯模型来生成用于实验验证的生物假设。 CDP中心的研究活动将得到研究生和本科生的补充 教育和一个以科学界和少数群体为服务对象的外联方案 特别是机构

The remarkable complexity of biological systems demands a systematic approach to their analysis. The goal of this proposal is to establish an MIT Center of Excellence in Cell Decision Processes (CDP) around an interdisciplinary team of cell biologists, computer scientists and microsystems engineers tackling the systems biology of protein networks and signal transduction in mammalian cells. The basic hypothesis of the CDP Center is that understanding cell decision processes requires the development of network models that combine quantitative rigor with molecular detail. These models will be hybrids containing highly specific representations of critical reactions and abstract representations of the system as a whole. Effective models will endure and capture the accumulation of knowledge over time in a rigorous and portable format. The CDP Center will follow a research paradigm that links systematic experiments and numerical modeling in a four-step feedback loop of manipulation-measurement-mining and modeling. The biological focus of the Center will be the signaling events that control apoptosis. The measurement of protein concentrations, modification state and activity will be undertaken for signaling molecules at many points in the apoptotic network. The measurements will then be analyzed using several modeling approaches ranging from highly specified to highly abstract. To collect sufficient data for systematic modeling, the CDP Center will automate and standardize biochemical methods, develop compact array-based assays and design novel microfabricated devices with integrated microfluidics and label-free sensors. To organize and systematize the data, inforrnatic methods will be developed that support rigorous approaches to inference. Finally, physico-chemical, structure-systems and Bayesian models will be used to generate biological hypothesis for experimental verification. The research activities of the CDP Center will be complemented by graduate and undergraduate education and by an outreach program targeted at the scientific community in general and minority-serving institutions in particular