RNA Origami Technology in Cell Systems

Descripción del proyecto

Papiroflexia de ARN para el control celular

La papiroflexia de ARN es un método de nanotecnología que aprovecha las propiedades naturales de plegamiento del ARN para construir nanoestructuras en dos y tres dimensiones. Estas estructuras modulables pueden adaptarse para crear dispositivos moleculares capaces de realizar funciones de detección, computación y activación dentro de células vivas. El proyecto RIBOTICS, financiado por el Consejo Europeo de Investigación, busca llevar este concepto un paso más allá y crear nanorrobots basados en ARN para la regulación sintética de procesos celulares. Los investigadores emplearán diseño asistido por ordenador para desarrollar constructos de ARN codificados genéticamente, con el fin de controlar la expresión génica y organizar las vías metabólicas en la levadura. Esta tecnología demuestra gran versatilidad y se espera que encuentre aplicaciones en biotecnología y medicina.

Objetivo

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.