Expanding the function and utility of nucleic acids

扩展核酸的功能和用途

• 批准号: RGPIN-2015-05806
• 负责人: Li, Yingfu
• 金额: $ 9.11万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=657526
• 关键词: Expanding; function; utility; nucleic; acids

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. ***

众所周知，核酸是地球上所有生物体的蓝图，也是现代生物学的基础。核酸--包括DNA和RNA --被反复证明具有其他才能，包括作为催化剂（酶）和分子侦探（受体）的能力。越来越多的天然和人造核酸具有有趣的催化或结合功能，它们的存在激发了许多学科的科学家研究它们的基本性质，并利用它们开发新概念以及化学，生物技术，材料科学，纳米技术和医学的各种应用。我的小组一直在研究三种不同类型的功能核酸：DNA酶，适体和核糖开关。DNA酶是一种人造的基于DNA的“分子引擎”，可以加速化学转化。适体是一种人造的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（如疾病的生物标志物）。核糖开关是一种基于RNA的细胞“分子开关”，它告诉细胞是否需要合成一种特定的分子来支持其生命活动。因此，DNA酶、核酸适体和核糖开关是获得基础知识和实际应用的重要分子。我们将在这个拟议的NSERC发现补助金计划中追求四个具体目标。首先，我们将建立一个多功能的，超灵敏的生物传感平台，整合适体作为刺激响应分子开关与强大的信号放大技术。第二，我们将开发DNA酶，催化一种重要的新化学反应，RNA甲基化，作为继续扩大DNA催化库的努力。第三，我们将开发基于核糖开关的生物传感器，使其易于检查活细胞中的分子功能。最后但并非最不重要的是，我们将设计复杂的基于DNA的纳米机器，将DNA适体和DNA酶作为重要的功能组件。预计通过这些研究，我们将产生关于DNA酶，适体和核糖开关的新知识，这反过来将导致科学家可以用来回答有关生物催化和分子识别的基本问题的新分子系统的发展。拟议的工作还将为开发生物分析应用创造新的方法，以便为加拿大人和世界各地的人民提供更安全的食品、更好的环境和更有效的诊断方法。此外，这笔赠款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。