Expanding the function and utility of nucleic acids

核酸-DNA和RNA-更为人所知的是地球上所有生物的蓝图和现代生物学的基础，它一再被证明具有其他生物天赋，包括充当催化剂(酶)和分子生物学探测器(受体)的能力。越来越多的天然和人造核酸被发现，它们具有耐人寻味的催化或结合功能，它们的存在激励了来自许多学科的科学家研究它们的基本性质，并利用它们来开发新的概念以及在化学、生物科技、材料科学、纳米技术和医学方面的不同应用。我的团队一直在研究三种不同类别的功能核酸：DNA酶、适配子和核糖开关。DNAzyme是一种人造的基于DNA的分子引擎，可以加快化学转化。适配子是一种人造DNA或RNA“分子探测器”，可以从复杂的分子混合物中精确定位特定的分子靶标(如疾病的生物标记物)。核糖开关是一种基于细胞RNA的分子开关，它告诉细胞它是否需要合成特定的分子来支持其生命活动。因此，DNAzyme、适配子和核糖开关是研究基础知识获取和实际应用的重要分子。我们将在这项拟议的NSERC发现拨款计划中追求四个具体目标。首先，我们将建立一个多功能、超灵敏的生物传感平台，将适配子作为刺激响应分子开关与强大的信号放大技术相结合。其次，我们将开发催化一种重要的新化学反应--RNA甲基化的DNAzyme，以继续扩大DNA的催化谱系。第三，我们将开发基于核糖开关的生物传感器，使检测活细胞的分子功能变得容易。最后但同样重要的是，我们将设计复杂的基于DNA的纳米机器，将DNA适配子和DNAzyme作为基本的功能组件。预计通过这些研究，我们将产生关于DNA酶、适配子和核糖开关的新知识，这反过来将导致新分子系统的开发，科学家可以利用这些系统来回答关于生物催化和分子识别的基本问题。拟议的工作还将创造新的方法，为加拿大人和世界各地的人民开发更安全的食品、更好的环境和更有效的诊断方法的生物分析应用程序。此外，这笔资金将使我的实验室能够培养有才华的下一代科学家，这将有助于确保加拿大未来在科学、技术和知识驱动的全球经济中的竞争力。

Better known as the blueprint of all living organisms on earth and the foundation of modern biology, nucleic acids - both DNA and RNA - have been repeatedly shown to have other talents, which include the ability to function as catalysts (enzymes) and molecular detectives (receptors). A growing number of natural and man-made nucleic acids with intriguing catalytic or binding functions have been discovered, and their existence has inspired scientists from many disciplines to investigate their fundamental properties and use them to develop new concepts as well as diverse applications in chemistry, biotechnology, materials science, nanotechnology and medicine. My group has been studying three different classes of functional nucleic acids: DNAzymes, aptamers and riboswitches. A DNAzyme is a man-made DNA-based "molecular engine" that can speed up a chemical transformation. An aptamer is a man-made DNA or RNA "molecular detective" that can pinpoint a specific molecular target (like a biomarker of a disease) from a complex molecular mixture. A riboswitch is a cellular RNA-based "molecular switch" that tells a cell whether it needs to synthesize a specific molecule for supporting its living activities. Therefore, DNAzymes, aptamers and riboswitches are important molecules to study for fundamental knowledge acquisition as well as for practical applications. We will pursue four specific aims within this proposed NSERC Discovery Grant program. First, we will establish a versatile, ultra-sensitive biosensing platform that integrates aptamers as stimuli-responsive molecular switches with a powerful signal amplification technique. Second, we will develop DNAzymes that catalyze an important new chemical reaction, RNA methylation, as an effort to continue the expansion of the catalytic repertoire of DNA. Third, we will develop riboswitch-based biosensors that make it easy to examine molecular functions in living cells. Last but not least, we will engineer intricate DNA-based nanomachines that incorporate DNA aptamers and DNAzymes as essential functional components. It is expected that through these studies, we will generate new knowledge about DNAzymes, aptamers and riboswitches, which in turn will lead to the development of new molecular systems that scientists can utilize to answer fundamental questions about biological catalysis and molecular recognition. The proposed work will also create new approaches towards developing bioanalytical applications for safer food, a better environment and more effective diagnostic methods for Canadians and people around the world. Furthermore, this grant will allow my laboratory to develop talented, next-generation scientists, which will help ensure Canada's future competitiveness in science, technology, and knowledge-driven global economy. ***