RIBOTICS · RNA Origami Technology in Cell Systems

Biomolecular nanotechnology aims at using the self-assembly principles of nature to create nanostructures and nanomachines for applications in biotechnology, medicine, and materials science. Advanced nanodevices, that sense inputs, do basic computations, and actuate functionality or movement within their nanoscale environment, are referred to as “nanorobots”. With advances in methods for prediction and design of RNA and protein structure, there is now a big opportunity to create complex biomolecular nanorobots. However, it is not clear how to combine multiple functional motifs and how to design the dynamical energy landscapes of molecular machines. In the RIBOTICS research proposal, I will address this challenge by the construction of RNA origami robots that sense, compute, and actuate in cellular environments with the goal of providing components for RNA-based synthetic regulation of living cells. To achieve this goal, we will: (1) Establish a platform for design and characterization of RNA origami robots by developing computer-aided design software and using advanced cryo-electron microscopy and tomography methods, (2) Develop genetically encoded RNA origami robots for control of gene expression and spatial organization of enzymes for metabolic engineering, (3) Develop xenonucleic acid (XNA) origami robots by studying the effects of chemical modifications on structure and function of RNA motifs for applications in controlled gene delivery and biosensing, (4) Develop RNA circuits for control of RNA origami robot systems in cells to develop RNA-based signal transduction pathways for control of metabolism and biosynthesis in S. cerevisiae yeast. If successful, this project will provide a better understanding of the design principles for biomolecular function and provide a general platform for the development of RNA robot and circuit technology in cell systems for broad applications in biotechnology and medicine.