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麻省理工学院细胞决策过程卓越中心（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，要理解单元决策过程，就需要开发网络模型 结合了联合收割机定量精确性和分子细节。这些模型将是混合体， 关键反应的表征和系统整体的抽象表征。有效模式 将忍受和捕捉知识的积累，随着时间的推移，在一个严格的和便携式的格式。 CDP中心将遵循一种研究范式，将系统实验和数值计算相结合。 采用操作-测量-挖掘-建模四步反馈回路建模。生物 该中心的重点将是控制细胞凋亡的信号事件。测量蛋白质 浓度、修饰状态和活性将在本发明的许多点上针对信号分子进行。 凋亡网络然后将使用几种建模方法分析测量结果， 从高度具体到高度抽象。 为了收集足够的数据进行系统建模，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测定和设计新颖的微加工装置， 集成微流体和无标记传感器。为了组织和系统化数据，信息方法将 开发支持严格推理方法的工具。最后，物理化学，结构系统和 贝叶斯模型将用于生成生物学假设以进行实验验证。 CDP中心的研究活动将由研究生和本科生补充 教育和针对一般科学界和少数群体服务的外联方案， 机构尤其

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