Adaptive Queueing in Intracellular Networks

蜂窝内网络中的自适应排队

• 批准号: 1463657
• 负责人: Lev Tsimring
• 金额: $ 160万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1463657&HistoricalAwards=false
• 关键词: Adaptive; Queueing; Intracellular; Networks

Rapid and coordinated response to environmental fluctuations and the ability to maintain function in a broad range of conditions is a key to survival in the biological world. Therefore, organisms employ complex regulatory strategies that combine sensitivity and robustness in response to environmental changes. One potential mechanism for such responsiveness that has emerged through recent studies of enzymatic networks is a queueing effect in protein abundances. The phenomenon appears to be widespread in biology. This research project employs mathematical modeling and synthetic biology to explore and better understand this mechanism and its role in biological functions.This project investigates a queueing effect in intracellular networks. As processing enzymes transition from underloaded to overloaded conditions, the corresponding protein abundances (queues) increase drastically, and in a highly coordinated fashion. A number of recent observations suggest that enzymatic networks are often poised near the balance point between underloaded and overloaded regimes where it makes them highly sensitive and responsive to transient environmental fluctuations. This phenomenon appears to be widespread in biology; furthermore it should be highly optimized to a broad range of environmental conditions by adaptive regulatory mechanisms. In this project, the investigators combine rigorous mathematical analysis with quantitative computational modeling and synthetic biology to pinpoint the mechanisms and probe the role of adaptive queueing in the dynamics of small gene circuits as well as large intracellular enzymatic networks in bacteria and yeast. The investigators make use of their combined expertise in queueing theory, stochastic kinetic modeling, design of robust synthetic gene circuits and microfluidic technology to elucidate and characterize the role of adaptive queueing as a fast and flexible signal transduction and regulatory mechanism in bacteria and higher organisms.

对环境波动的快速协调反应以及在各种条件下维持功能的能力是生物世界生存的关键。 因此，生物体采用复杂的调节策略，结合敏感性和鲁棒性来响应环境变化。 最近对酶网络的研究发现，这种响应性的一种潜在机制是蛋白质丰度的排队效应。 这种现象在生物学中似乎很普遍。 该研究项目采用数学模型和合成生物学来探索和更好地理解这种机制及其在生物功能中的作用。该项目研究细胞内网络中的排队效应。 随着加工酶从欠载条件转变为过载条件，相应的蛋白质丰度（队列）急剧增加，并且以高度协调的方式。 最近的一些观察表明，酶网络通常处于负载不足和过载状态之间的平衡点附近，这使得它们对瞬态环境波动高度敏感和敏感。 这种现象在生物学中似乎很普遍。此外，应通过适应性监管机制对其进行高度优化，以适应广泛的环境条件。 在该项目中，研究人员将严格的数学分析与定量计算模型和合成生物学结合起来，以查明机制并探讨自适应排队在细菌和酵母中的小基因电路以及大型细胞内酶网络的动态中的作用。 研究人员利用他们在排队理论、随机动力学模型、强大的合成基因电路设计和微流体技术方面的综合专业知识来阐明和表征自适应排队作为细菌和高等生物中快速、灵活的信号转导和调节机制的作用。

项目成果

ON CONSTRAINED LANGEVIN EQUATIONS AND (BIO)CHEMICAL REACTION NETWORKS

• DOI: 10.1137/18m1190999
• 发表时间: 2019-01-01
• 期刊: MULTISCALE MODELING & SIMULATION
• 影响因子: 1.6
• 作者: Anderson, David F.;Higham, Desmond J.;Williams, Ruth J.
• 通讯作者: Williams, Ruth J.