Programmable, self-regulated DNA and RNA nanomachines

点击翻译按钮获取中文摘要

The historically unprecedented developments of nanoscience and nanotechnology promise to revolutionize many fields including electronics, biomaterials, energy production, and medicine. Artificial nanomachines similar to the ones observed in living organisms, for example, could be conceived in a near future to perform rapid environmental and human molecular diagnosis, to develop molecular computers, or to deliver drug in the vicinity of pathogens or tumor cells. Many challenges, however, remain before this vision becomes reality. Top-down approaches for the construction of miniaturized devices have reached their limits, due to fundamental and practical restrictions below sizes of twenty nanometers. On the other hand, the bottom-up approach, which employs molecules as nanometer-scale building blocks to construct nanomachines still remains at an embryonic state with chemists struggling to design molecular machines with any commercial value. As a result, nanoengineers are urgently awaiting the development of new approaches that will enable the design of useful nanomachines.Dr. Vallée-Bélisle's research will pave the way towards achieving this goal by engineering artificial DNA or RNA nanomachines that mimic the ones developed by living organisms. Relying on his strong expertise on natural nanomachines (Ph.D. in biochemistry - protein folding mechanisms) and his expertise in DNA engineering (recently acquired during his postdoc at the Center for Bioengineering at University of California, Santa Barbara), Dr. Vallée-Bélisle focuses his current research program on the design and thermodynamic characterization of simplified mimics of natural nanomachines using highly designable DNA and RNA scaffolds and artificially selected aptamers. Beyond enabling the detailed thermodynamic analysis of these systems, his nanomachines will also be adapted for various applications in analytical chemistry, pharmacology, and molecular computing. Dr. Vallée-Bélisle’s multidisciplinary lab combines state-of-the-art techniques in DNA design and synthesis, various biophysical spectroscopic techniques for characterizing and optimizing nanomachines, as well as different platforms allowing custom fitting of nanomachines to real life applications. Dr. Vallée-Bélisle's approach is unique in Canada and consists mostly in the: (1) de novo DNA switch and nanomachines design using nucleic acid modeling programs to predict switching thermodynamics; (2) synthesis and purification of DNA machines; (3) thermodynamics and kinetic characterization of nanomachines to allow further optimization of their activity; and (4) application of his nanomachines for the development of rapid diagnostic tests (animal, environment and humans) and self-regulated nanomachines for smart delivery of drugs. The groundbreaking technologies built in this grant program will offer means to create a new generation of technologies in Canada with a huge commercialization potential.in biotechnology, an economic sector of great importance in Canada. The requested grant will also enable Dr. Vallée-Bélisle to train nine highly-skilled scientists that will shape the workforce of these important emergent industrial sectors.