Transitions: Evolving our Understanding of Dynamic RNA Folding and Function

转变：加深我们对动态 RNA 折叠和功能的理解

• 批准号: 2310382
• 负责人: Julius Lucks
• 金额: $ 75万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2310382&HistoricalAwards=false
• 关键词: Transitions; Evolving; our; Understanding; Dynamic

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.

RNA分子是DNA分子的紧密化学表亲，在制定所有生物的生命遗传学指导中起着核心作用，并且在生物技术中起着越来越重要的作用。这项研究将揭示新的基本原理，以解释RNA分子的序列如何确定其功能。通过更改其序列的更改可以提高我们设计基于RNA的生物技术的能力，从而对RNA分子的功能进行更深入的了解，以应对可持续性，生物制造和健康方面的全球挑战。该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，这些课程在尖端的合成生物学教学方法中教授这项研究的概念，这些教学方法正在全国范围内被分散。该项目的主要目标是为PI和研究团队提供了在有指导性的构成物理学的概念和非统计学的工具中，以提供新的培训，以实现摩尔的概念和非统计学的工具。折叠成生物系统中的特定形状。这项研究的一个焦点是研究RNA折叠过程的动力学如何通过RNA序列变化来发展以满足特定功能目标，例如调节基因表达。该项目分为三个目标。第一个将在专业发展期间进行，PI将在定向进化领域中学习背景理论，实验和数据分析方法，以及非平衡的统计物理学方法，以模拟动态分子折叠，通过实践指导，课程工作，实验室培训和协作互动的结合。第二个将使用此训练进行研究，以发现将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械和进化原理，并在生物系统中与RNA功能。第三个将使用这些原则与指示进化一起发现的这些原则，以通过基于RNA的诊断技术的发展来应对诸如全球水危机等社会挑战的工程综合生物学系统。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子优点和广泛的影响来评估NSF的法定任务，并被认为是值得的支持。