CAREER: Biochemical Reaction Systems: from Structure to Dynamics

这个CAREER奖支持的项目将使用网络数学来了解活细胞如何保持健康的营养平衡，如铁。 在健康的细胞中，许多化学反应一直在发生。 科学家们认为这些反应形成了一个网络，就像一个接线图，连接电线描述了营养物质和代谢物通过细胞化学反应的运动。 了解整个线路图对于了解单个营养素的命运并不是必要的，但是许多相互关联的电路使得很难只分离出对某些活动重要的部分，例如维持铁水平。这项研究将使用数学技术（特别是代数几何和动力学系统）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。 作为研究项目的补充，将围绕定向阅读计划开展教育活动，在该计划中，本科生将在研究生导师的帮助下获得阅读和演示数学的经验。在生命系统中观察到的动态远远超过其部分的总和。 因此，系统生物学试图了解生物成分如何聚集在一起产生紧急的系统级行为。 目前系统生物学的一个瓶颈是缺乏将系统结构与涌现行为联系起来的数学理论。 因此，本项目将开发一种适合生物网络的反应系统理论。 研究人员将建立在她最近的工作，帮助澄清如何双稳态和其他现象出现在现实生活中的系统。 这里的目的是发现反应系统中多平稳性的新标准，并回答当新的组件被添加到网络时，Hopf分叉被保留的问题。 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中的双稳态和振荡能力，并确定铁运输网络的哪些组成部分保持细胞铁水平的严格调节。总的来说，该研究将产生非常适合分析生命系统中出现的一大类网络的结果。该奖项反映了NSF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。

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.