Programmable, self-regulated DNA and RNA nanomachines

纳米科学和纳米技术的空前发展有望彻底改变许多领域，包括电子，生物材料，能源生产和医学。例如，在不久的将来，可以设想类似于在生物体中观察到的人工纳米机器，以进行快速的环境和人类分子诊断，开发分子计算机，或在病原体或肿瘤细胞附近提供药物。然而，在这一愿景成为现实之前，仍存在许多挑战。由于低于20纳米的基本和实际限制，用于构建小型化设备的自上而下的方法已经达到了极限。另一方面，自下而上的方法，即利用分子作为纳米尺度的构建模块来构建纳米机器，仍然处于萌芽状态，化学家们正在努力设计具有商业价值的分子机器。因此，纳米工程师们迫切地等待着新方法的发展，这将使有用的纳米机器的设计。Vallée-Bélisle博士的研究将为实现这一目标铺平道路，方法是设计人工DNA或RNA纳米机器，模仿生物体开发的机器。凭借他在天然纳米机器方面的强大专业知识（博士学位），Vallée-Bélisle博士在生物化学-蛋白质折叠机制方面拥有丰富的经验，并在DNA工程方面拥有丰富的专业知识（最近在圣巴巴拉的加州大学生物工程中心做博士后期间获得），他目前的研究项目集中在使用高度可设计的DNA和RNA支架以及人工选择的适体设计和热力学表征天然纳米机器的简化模拟物。除了能够对这些系统进行详细的热力学分析外，他的纳米机器还将适用于分析化学，药理学和分子计算中的各种应用。** Vallée-Bélisle博士的多学科实验室结合了DNA设计和合成中最先进的技术，用于表征和优化纳米机器的各种生物物理光谱技术，以及允许纳米机器定制适配真实的生活应用的不同平台。Vallée-Bélisle博士的方法在加拿大是独一无二的，主要包括：（1）从头DNA开关和纳米机器设计，使用核酸建模程序来预测开关热力学;（2）DNA机器的合成和纯化;（3）纳米机器的热力学和动力学表征，以进一步优化其活性;以及（4）他的纳米机器在开发快速诊断测试（动物，环境和人类）和自我调节纳米机器智能药物输送方面的应用。 在这项赠款计划中建立的开创性技术将提供在加拿大创造新一代技术的手段，具有巨大的商业potential.in生物技术，这是加拿大非常重要的经济部门。 申请的拨款还将使Vallée-Bélisle博士能够培训9名高技能的科学家，这些科学家将塑造这些重要新兴工业部门的劳动力。

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.