EAGER: Toward unifying theories of living systems

渴望：统一生命系统理论

• 批准号: 2232049
• 负责人: Olga Dudko
• 金额: $ 30万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2232049&HistoricalAwards=false
• 关键词: EAGER; Toward; unifying; theories; living

The goal of this project is to find physical principles that unify our understanding of the seemingly unrelated and strikingly diverse membrane-fusion-mediated processes in biology. These processes include the invasion of a host cell by an enveloped virus, the rapid and precisely timed communication between neurons, the fertilization of an egg by sperm, skeletal muscle formation, carcinogenesis, intracellular trafficking, and cell secretion. The results of this project will serve as an important step towards addressing the formidable complexity of living systems through simplifying yet powerfully predictive physical theories. While such simplifying and unifying approaches are common in physics in the contexts of inanimate matter, they are underdeveloped in many areas of biology. The educational and outreach activities associated with this project will promote the advancement of physics research that straddles traditional subject boundaries and the recruitment of young scientists from all segments of society to the field of biological physics. This project will introduce students from biology backgrounds to the enabling power of quantitative approaches in scientific discovery and will facilitate the use of physics by biology students in their research. These activities will encourage early engagement with research as a catalyst in awakening and maintaining interest of undergraduate students in science. Membrane fusion refers to the topology-changing process during which the membrane surrounding an independent biological entity (an enveloped virus, a vesicle, or a cell) recombines with the membrane of a target cell such that their contents can mix. Membrane fusion-mediated processes are realized by diverse entities, are regulated by structurally unrelated molecules, respond to different triggers, and occur on different timescales. Yet there are hints of unifying principles: in all these processes, the overcoming of the high energy barriers that hinder fusion is facilitated by protein conformational transitions in response to a trigger, which allows the biological processes that occur by fusion to proceed on time scales as short as a fraction of a millisecond. This project aims to capture these principles in the form of a unifying analytical theory rooted in nonequilibrium statistical mechanics that is reasonably simple and abstract yet generates concrete, testable predictions. Uncovering the unifying principles of living systems is crucial for the understanding of the mechanisms by which evolution drives living systems toward their functional behavior. This project is jointly funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences and the Physics of Living Systems in the Division of Physics.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.

该项目的目的是找到物理原则，以统一我们对生物学中看似无关和多样化的膜融合介导的过程的理解。这些过程包括被包膜病毒对宿主细胞的侵袭，神经元之间的快速而精确的定时通信，精子的卵受精，骨骼肌形成，致癌，细胞内运输和细胞分泌。该项目的结果将是通过简化但有力的预测物理理论来解决生活系统的强大复杂性的重要一步。尽管这种简化和统一的方法在无生命物质的背景下在物理学中很常见，但它们在许多生物学领域都欠发达。与该项目相关的教育和外展活动将促进物理研究的进步，这些研究跨越了传统的主题界限，并从社会各个细分市场招募了年轻科学家到生物物理学领域。该项目将向生物学背景的学生介绍科学发现中定量方法的能力，并促进生物学学生在研究中使用物理学的能力。这些活动将鼓励尽早参与研究，以催化唤醒和维持科学学院的兴趣。膜融合是指改变拓扑的过程，在此过程中，围绕独立生物实体的膜（包围病毒，囊泡或细胞）与靶细胞的膜重新组合，使其含量可以混合。膜融合介导的过程由不同的实体实现，受结构不相关的分子调节，对不同的触发器响应，并发生在不同的时间尺度上。然而，有一些统一原则的迹象：在所有这些过程中，克服高能障碍物，即响应触发蛋白质构象转变促进了促进融合的促进，从而使触发的生物学过程允许融合所发生的生物学过程，以便在时间尺度上以一小部分的速度进行时间尺度。该项目的目的是以一种扎根于非平衡统计力学的统一分析理论的形式捕获这些原则，该理论是相当简单且抽象的，但产生了具体的，可测试的预测。揭示生命系统的统一原则对于理解进化使生命系统朝着其功能行为的机制的理解至关重要。该项目由分子和细胞生物科学的划分的分子生物物理学群集以及物理学的生物学分类组合资助。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。