Programmable, self-regulated DNA and RNA nanomachines

可编程、自我调节的 DNA 和 RNA 纳米机器

• 批准号: RGPIN-2014-06403
• 负责人: ValléeBélisle, Alexis
• 金额: $ 2.55万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612200
• 关键词: Programmable; self; regulated; DNA; RNA

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.

纳米科学和纳米技术在历史上前所未有的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与在生物体中观察到的类似的人造纳米机器来执行快速的环境和环境控制。然而，在这种自上而下的微型设备构建方法达到其极限之前，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输送药物仍然存在许多挑战。对基本和另一方面，使用分子作为纳米级构建块来构建纳米机器的自下而上的方法仍然处于萌芽状态，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，纳米工程师迫切等待新方法的开发，以设计有用的纳米机器。 Vallée-Bélisle 博士的研究将为通过设计模仿生物体开发的人工 DNA 或 RNA 纳米机器（生物化学博士 - 蛋白质折叠机制）来实现这一目标铺平道路。 Vallée-Bélisle 博士凭借其在 DNA 工程方面的专业知识（最近在加州大学圣塔芭芭拉分校生物工程中心做博士后期间获得），专注于他的研究目前的研究计划是使用高度可设计的 DNA 和 RNA 支架以及人工选择的适体来设计和热力学表征自然纳米机器的简化模拟，除了能够对这些系统进行详细的热力学分析之外，他的纳米机器还将适用于分析化学中的各种应用，药理学和分子计算。 Vallée-Bélisle 博士的多学科实验室结合了最先进的 DNA 设计和合成技术、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适合现实生活应用的不同平台。 -Bélisle 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转换的从头 DNA 开关和纳米机器设计热力学；(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；(4) 应用纳米机器开发快速诊断测试（动物、环境和人类） ）和用于智能输送药物的自我调节纳米机器，该资助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。加拿大。所申请的赠款还将帮助瓦莱-贝利勒博士培训九名高技能科学家，他们将塑造这些重要新兴工业部门的劳动力。