Transitions: Evolving our Understanding of Dynamic RNA Folding and Function

RNA分子是DNA分子的化学近亲，在制定所有生物体的生命遗传指令方面发挥着核心作用，并在生物技术中发挥着越来越重要的作用。这项研究将揭示新的基本原理，解释RNA分子的序列如何决定其功能。更深入地了解如何通过改变RNA分子的序列来编程其功能，有望增强我们设计基于RNA的生物技术的能力，以应对可持续发展、生物制造和健康方面的全球挑战。这个项目的其他好处包括在这项研究中培训和整合研究生和本科生，并创建新的课程，在国家正在传播的尖端合成生物学教学方法中教授这项研究的概念。这个项目的一个主要目标是为PI和研究团队提供定向进化和非平衡统计物理的概念和工具的应用培训，以创建新的视角来研究RNA分子如何通过折叠成特定形状在生物系统中发挥作用。本研究的重点是探讨RNA折叠过程的动力学如何通过RNA序列的变化来满足特定的功能目标，如调节基因表达。该项目分为三个目标。第一次将在专业发展阶段进行，在那里，PI将学习定向进化领域的背景理论、实验和数据分析方法，以及通过实践指导、课程工作、实验室培训和协作互动相结合的非平衡统计物理方法来模拟动态分子折叠。第二个将利用这种培训来进行研究，以揭示将RNA序列与RNA合成过程中发生的动态RNA折叠过程联系起来的机制和进化原理，以及生物系统中的RNA功能。第三个奖项将使用这些发现的原理，结合定向进化，通过开发基于RNA的诊断技术来设计合成生物学系统，以应对全球水资源危机等社会挑战。该奖项反映了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。

RNA molecules, close chemical cousins of DNA molecules, play central roles in enacting the genetic instructions of life in all organisms, and are playing increasingly important roles in biotechnologies. This research will uncover new fundamental principles that explain how the sequence of an RNA molecule determines its function. A deeper understanding of how the function of RNA molecules can be programmed through changes to their sequence promises to enhance our ability to engineer RNA-based biotechnologies that address global challenges in sustainability, biomanufacturing, and health. Additional benefits of this project include training and integrating graduate and undergraduate students in this research and creating new curriculum that teach concepts of this research within cutting-edge synthetic biology pedagogical approaches that are being disseminated nationally.A major goal of this project is to provide the PI and research team applied training in the concepts and tools of directed evolution and non-equilibrium statistical physics to create new perspectives to studying how RNA molecules function through folding into specific shapes within biological systems. A focal point of this research is to investigate how the dynamics of RNA folding processes can evolve through RNA sequence changes to meet specific functional goals such as regulating gene expression. The project is divided into three objectives. The first will take place during a professional development period, where the PI will learn the background theory, experiments, and data analysis approaches in the field of directed evolution, as well as non-equilibrium statistical physics approaches to model dynamic molecular folding, through a combination of hands-on mentoring, coursework, laboratory training and collaborative interactions. The second will use this training to perform research to uncover mechanistic and evolutionary principles that link RNA sequence, to dynamic RNA folding processes that occur during RNA synthesis, to RNA function in biological systems. The third will use these principles discovered, in combination with directed evolution, to engineer synthetic biology systems that address societal challenges such as the global water crisis through the development of RNA-based diagnostic technologies.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.