EAGER: Toward unifying theories of living systems

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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.