EAGER: Toward unifying theories of living systems

这个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和惊人不同的膜融合中介过程的理解。这些过程包括被包裹的病毒入侵宿主细胞，神经元之间快速和精确的通讯，精子受精，骨骼肌形成，癌症发生，细胞内运输和细胞分泌。这个项目的结果将是通过简化但具有强大预测性的物理理论，朝着解决生命系统的巨大复杂性迈出的重要一步。虽然在无生命物质的情况下，这种简化和统一的方法在物理学中很常见，但在生物学的许多领域中，它们并不发达。与该项目相关的教育和宣传活动将促进跨越传统学科界限的物理学研究的发展，并促进从社会各阶层招募青年科学家进入生物物理学领域。这个项目将向生物学背景的学生介绍量化方法在科学发现中的能力，并将促进生物学学生在他们的研究中使用物理学。这些活动将鼓励及早参与研究，作为唤醒和保持本科生对科学的兴趣的催化剂。膜融合是指一个独立的生物实体(被包裹的病毒、囊泡或细胞)周围的膜与靶细胞的膜重组，从而使它们的内容物可以混合的拓扑变化过程。膜融合介导的过程由不同的实体实现，受结构无关的分子调控，对不同的触发因素做出反应，并在不同的时间尺度上发生。然而，也有统一原则的迹象：在所有这些过程中，阻碍融合的高能障碍的克服是通过对触发做出反应的蛋白质构象转变来促进的，这使得通过融合发生的生物过程可以在短至几分之一毫秒的时间尺度上进行。这个项目旨在以一种植根于非平衡统计力学的统一分析理论的形式捕捉这些原理，该理论相当简单和抽象，但产生具体的、可检验的预测。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。这个项目是由分子和细胞生物科学部的分子生物物理组和物理部的生命系统物理学共同资助的。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.