EMT/BSSE: Hierarchical representation and simulation of modular cellular systems

EMT/BSSE：模块化蜂窝系统的分层表示和模拟

• 批准号: 0829788
• 负责人: James Faeder
• 金额: $ 30.18万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0829788&HistoricalAwards=false
• 关键词: EMT; BSSE; Hierarchical; representation; simulation

Biological systems are the product of an evolutionary process of random tinkering and selection that resulted in unexpected and non-intuitive ?engineering? solutions to dynamically varying conditions. Thus, biological systems are robust, adaptive and evolvable information processing systems that operate asynchronously and in parallel on multiple scales. The examination and characterization of the design principles of biological circuits has the potential to revolutionize biology, medicine and the way computing and communication systems are built. This project is pioneering important advances at the interface between biology and computation by pursuing two complementary goals: (1) to develop a modular, parallel-ready simulator to replicate the multi-scalar architecture of complex biological systems; (2) to discover key design principles relevant to information processing systems in general by reproducing biological design in silico. Information processing by cells encompasses multiple scales connecting molecular events to phenotypes. Current simulation techniques have limited multi-scale and modular capabilities, resulting in models that describe only a single feature of a given system and miss the relationships between architecture, function and behavior. This research effort addresses these limitations by representing biological systems as a hierarchy of functional executable modules. The design of the platform obeys four basic principles: 1) components are objects; 2) objects are governed by rules; 3) rules include some degree of stochasticity; and 4) objects and rules are organized in functional and spatial modules that compose a hierarchy. The development of the new platform is driven by the construction of simulations of key biological model systems with an unprecedented scope and precision, such as bacterial chemotaxis, epidermal growth factor receptor signaling, the acute inflammatory response, and parallel processing by bacterial colonies. The reproduction of these biological systems in silico is providing insights into their design principles, which in turn advances the future design and implementation of distributed technological systems.

生物系统是随机修补和选择的进化过程的产物，导致了意想不到的、非直观的“工程”。动态变化条件的解决方案。因此，生物系统是鲁棒的、自适应的和可进化的信息处理系统，可以在多个尺度上异步和并行运行。对生物电路设计原理的检查和表征有可能彻底改变生物学、医学以及计算和通信系统的构建方式。该项目通过追求两个互补的目标，在生物学和计算之间的接口方面取得了重要进展：（1）开发模块化、并行就绪的模拟器来复制复杂生物系统的多标量架构； (2) 通过在计算机中再现生物设计来发现与一般信息处理系统相关的关键设计原则。细胞的信息处理涵盖将分子事件与表型连接起来的多个尺度。当前的仿真技术的多尺度和模块化能力有限，导致模型只能描述给定系统的单个特征，而忽略了架构、功能和行为之间的关系。这项研究工作通过将生物系统表示为功能可执行模块的层次结构来解决这些限制。平台的设计遵循四个基本原则：1）组件就是对象； 2）对象受规则约束； 3）规则包含一定程度的随机性； 4) 对象和规则被组织在构成层次结构的功能和空间模块中。新平台的开发是通过以前所未有的范围和精度构建关键生物模型系统的模拟来推动的，例如细菌趋化性、表皮生长因子受体信号传导、急性炎症反应以及细菌菌落的并行处理。这些生物系统在计算机中的再现提供了对其设计原理的见解，这反过来又推动了分布式技术系统的未来设计和实现。