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CAREER: Biochemical Reaction Systems: from Structure to Dynamics

职业：生化反应系统：从结构到动力学

基本信息

批准号：
1752672
负责人：
Anne Shiu
金额：
$ 41.53万
依托单位：
Texas A&M University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1752672&HistoricalAwards=false
关键词：
CAREER Biochemical Reaction Systems Structure

项目摘要

The project supported under this CAREER award will use the mathematics of networks to understand how living cells maintain a healthy balance of nutrients, like iron. In healthy cells, many chemical reactions take place all the time. Scientists think of these reactions as forming a network, like a wiring diagram, with connecting wires describing the movement of nutrients and metabolites through a cell's chemical reactions. Knowing the entire wiring diagram is not necessary for understanding the fate of individual nutrients, but the many interconnected circuits make it difficult to isolate only the part of the diagram important for certain activities, such as maintaining iron levels. This research will use mathematical techniques (specifically, algebraic geometry and dynamical systems) to find the simplest components in a reaction network that allow a cell to exhibit observed behaviors. Results will be tested using laboratory observations of how yeast cells manage and transport iron. Complementing the research projects will be educational activities centered around a Directed Reading Program in which undergraduate students will gain experience reading and presenting mathematics with the help of graduate-student mentors.The dynamics observed in living systems is much more than the sum of its parts. Systems biology, therefore, seeks to understand how biological components come together to generate emergent, systems-level behavior. A current bottleneck in systems biology is the lack of mathematical theory relating system structure to emergent behavior. Accordingly, this project will develop a theory of reaction systems tailored to biological networks. The investigator will build on her recent work that has helped clarify how bistability and other phenomena emerge in real-life systems. The aims here are to discover new criteria for multistationarity in reaction systems, and to answer the question of when Hopf bifurcations are preserved when new components are added to a network. These results will be used to answer important biological questions pertaining to how cells process information and how iron levels are maintained within cells. Specifically, the aims are to investigate the capacity for bistability and oscillations in phosphorylation networks, and to determine which components of iron-trafficking networks keep cellular-iron levels tightly regulated. Overall, the research will generate results well-suited to analyzing a large class of networks arising in living systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目将使用网络的数学来理解活细胞如何维持健康的营养平衡，比如铁。在健康细胞中，许多化学反应每时每刻都在发生。科学家们认为，这些反应形成了一个网络，就像接线图一样，通过连接线描述细胞化学反应中营养物质和代谢物的运动。了解整个接线图对于了解单个营养素的命运是没有必要的，但是许多相互连接的电路使得仅隔离对某些活动（如维持铁水平）重要的部分变得困难。这项研究将使用数学技术（特别是代数几何和动力系统）来找到反应网络中最简单的组件，这些组件允许细胞表现出观察到的行为。结果将使用酵母细胞如何管理和运输铁的实验室观察进行测试。与研究项目相辅相成的是以指导阅读计划为中心的教育活动，在该计划中，本科生将在研究生导师的帮助下获得阅读和展示数学的经验。在生命系统中观察到的动力学远不止其各部分的总和。因此，系统生物学试图理解生物成分如何聚集在一起产生紧急的系统级行为。系统生物学目前的一个瓶颈是缺乏将系统结构与突现行为联系起来的数学理论。因此，该项目将发展一种适合生物网络的反应系统理论。这位研究者将在她最近的研究基础上进一步阐明双稳性和其他现象是如何在现实系统中出现的。这里的目的是发现反应系统多平稳的新准则，并回答当新组分加入网络时Hopf分岔何时保留的问题。这些结果将用于回答有关细胞如何处理信息以及细胞内铁水平如何维持的重要生物学问题。具体来说，目的是研究磷酸化网络的双稳定性和振荡能力，并确定铁运输网络的哪些组成部分严格调节细胞铁水平。总的来说，这项研究将产生非常适合于分析生命系统中产生的大型网络的结果。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。