Programmable, self-regulated DNA and RNA nanomachines

纳米科学和纳米技术的史无前例的发展有望给包括电子、生物材料、能源生产和医学在内的许多领域带来革命性的变化。例如，在不久的将来，可以构思出类似于在活体中观察到的人工纳米机器，以执行快速的环境和人类分子诊断，开发分子计算机，或者在病原体或肿瘤细胞附近输送药物。然而，在这一愿景成为现实之前，还有许多挑战。由于20纳米以下的基本和实际限制，构建小型化设备的自上而下的方法已经达到了它们的极限。另一方面，使用分子作为纳米级构建块来构建纳米机器的自下而上方法仍处于萌芽状态，化学家们正在努力设计具有任何商业价值的分子机器。因此，纳米工程师正迫切地等待新方法的开发，这些方法将使有用的纳米机器的设计成为可能。 瓦莱-贝莱尔博士的研究将通过设计人造DNA或RNA纳米机器来模仿活生物开发的机器，从而为实现这一目标铺平道路。凭借他在天然纳米机器方面的深厚专业知识(生物化学-蛋白质折叠机制博士学位)和DNA工程专业知识(最近在加州大学圣巴巴拉分校生物工程中心博士后期间获得)，Vallée-Bélyle博士目前的研究计划专注于使用高度可设计的DNA和RNA支架以及人工选择的适配子来设计和表征简化的自然纳米机器模拟物。除了能够对这些系统进行详细的热力学分析外，他的纳米机器还将用于分析化学、药理学和分子计算的各种应用。 瓦莱-贝莱尔博士的多学科实验室结合了DNA设计和合成方面的最先进技术、用于表征和优化纳米机器的各种生物物理光谱技术，以及允许将纳米机器定制安装到现实生活应用中的不同平台。瓦莱-贝莱尔博士的方法在加拿大是独一无二的，主要包括：(1)使用核酸建模程序预测开关热力学的从头DNA开关和纳米机器设计；(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，以便进一步优化其活性；以及(4)应用他的纳米机器开发快速诊断测试(动物、环境和人类)和智能给药的自我调节纳米机器。这项赠款计划中建立的突破性技术将为加拿大创造具有巨大商业化潜力的新一代技术提供手段。生物技术是加拿大非常重要的经济部门。申请的拨款还将使瓦莱-贝莱尔博士能够培训9名高技能的科学家，这些科学家将塑造这些重要的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.