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，导致了意想不到的和非直观的？工程学？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，其在多个尺度上异步地和并行地操作。生物电路设计原理的研究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）开发一个模块化，并行就绪的模拟器，以复制复杂生物系统的多标量架构;（2）通过计算机复制生物设计，发现与信息处理系统相关的关键设计原则。细胞的信息处理包括将分子事件与表型联系起来的多个尺度。当前的仿真技术具有有限的多尺度和模块化能力，导致模型仅描述给定系统的单个特征，而忽略了体系结构、功能和行为之间的关系。这项研究工作解决了这些局限性，代表生物系统作为一个层次结构的功能可执行模块。平台的设计遵循四个基本原则：1）组件是对象; 2）对象由规则管理; 3）规则包含一定程度的随机性; 4）对象和规则被组织在组成层次结构的功能和空间模块中。新平台的开发是由构建具有前所未有的范围和精度的关键生物模型系统的模拟驱动的，例如细菌趋化性，表皮生长因子受体信号传导，急性炎症反应和细菌菌落的并行处理。这些生物系统的计算机复制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。