Transitions: Evolving our Understanding of Dynamic RNA Folding and Function

Northwestern University, Evanston IL

Investigators

Abstract

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.