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.

该项目的目标是找到物理原理，统一我们对生物学中看似无关且惊人多样的膜融合介导过程的理解。这些过程包括包膜病毒对宿主细胞的入侵、神经元之间快速而精确的定时通讯、精子对卵子的受精、骨骼肌形成、致癌、细胞内运输和细胞分泌。该项目的结果将成为通过简化但具有强大预测性的物理理论来解决生命系统的巨大复杂性的重要一步。虽然这种简化和统一的方法在无生命物质的物理学中很常见，但它们在生物学的许多领域都不发达。与该项目有关的教育和外联活动将促进跨越传统学科界限的物理学研究的发展，并从社会各阶层招募年轻科学家从事生物物理学领域的工作。该项目将向生物学背景的学生介绍定量方法在科学发现中的作用，并将促进生物学学生在研究中使用物理学。这些活动将鼓励早期参与研究，作为唤醒和保持本科生对科学兴趣的催化剂。膜融合是指拓扑变化过程，在此过程中，包围独立生物实体（包膜病毒、囊泡或细胞）的膜与靶细胞的膜重组，使得它们的内容物可以混合。膜融合介导的过程由不同的实体实现，由结构上不相关的分子调节，对不同的触发器作出反应，并在不同的时间尺度上发生。然而，在所有这些过程中，都存在一些统一的原则：在所有这些过程中，阻碍融合的高能障碍的克服是由蛋白质构象转变响应触发而促进的，这使得通过融合发生的生物过程在短至毫秒的时间尺度上进行。该项目旨在以一种统一的分析理论的形式来捕捉这些原则，该理论植根于非平衡统计力学，相当简单和抽象，但可以产生具体的，可测试的预测。揭示生命系统的统一原则对于理解进化驱动生命系统走向其功能行为的机制至关重要。该项目由分子和细胞生物科学部的分子生物物理学小组和物理学部的生命系统物理学共同资助。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。