Functional Nucleic Acids: Characterization, Structure and Applications

功能性核酸：表征、结构和应用

• 批准号: 238562-2013
• 负责人: Johnson, Philip
• 金额: $ 2.62万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629979
• 关键词: Functional; Nucleic; Acids; Characterization; Structure

Nucleic acids are tremendously versatile molecules. Aside from their role in information storage and transfer, DNA and RNA play active roles as functional molecules. They can act as catalysts, participate in ligand binding and play a role as material for building nanoscale molecular devices. However, functional nucleic acids are often thought of as a black box. The fine details of how these types of molecules work is not known. Their structures, how they interact with other molecules, how they fold into an active molecule are poorly understood. Moreover, the design of new applications that use functional nucleic acids are hindered by our lack of knowledge of how these molecules work. Research in my laboratory aims to tackle this lack of understanding and learn how functional nucleic acid molecules perform their complex functions. As an additional benefit, as we better understand the details of how functional nucleic acids carry out their tasks, we will use this knowledge to engineer new applications and to design structures with new binding abilities. As a model system for discovering how functional nucleic acids work, my laboratory is focused on understanding how the cocaine-binding DNA aptamer operates. Specific projects detailed in this proposal include determining the structure of the cocaine-binding aptamer bound to its target ligand, cocaine. We will use a combination of nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) techniques to determine the three-dimensional structure of the free and ligand-bound aptamer. We will also study the binding of the cocaine aptamer to a range of ligands and in a range of conditions in order to understand how the aptamer binds its target and to discover new aptamer-ligand pairs. Another goal of my research is to use the cocaine aptamer to form chains that assemble upon ligand binding. Together, my proposed research will shed light into how a functional nucleic acid works and apply this knowledge into new applications.

核酸是非常多用途的分子。DNA和RNA除了在信息存储和传递中发挥作用外，还作为功能分子发挥着积极的作用。它们可以作为催化剂，参与配体结合，并作为构建纳米级分子器件的材料。然而，功能性核酸通常被认为是一个黑盒子。这些分子如何工作的细节尚不清楚。它们的结构，它们如何与其他分子相互作用，它们如何折叠成活性分子，人们知之甚少。此外，由于我们缺乏对这些分子如何工作的了解，使用功能性核酸的新应用的设计受到了阻碍。我实验室的研究旨在解决这种缺乏理解的问题，并了解功能性核酸分子如何发挥其复杂功能。作为一个额外的好处，随着我们更好地了解功能性核酸如何执行其任务的细节，我们将利用这些知识来设计新的应用和设计具有新的结合能力的结构。作为发现功能性核酸如何工作的模型系统，我的实验室专注于了解可卡因结合DNA适体是如何运作的。本提案中详细介绍的具体项目包括确定与其靶配体可卡因结合的可卡因结合适体的结构。我们将使用核磁共振（NMR）和小角度x射线散射（SAXS）技术的组合来确定自由和配体结合的适体的三维结构。我们还将研究可卡因适配体在一系列条件下与一系列配体的结合，以了解适配体如何与靶标结合并发现新的适配体-配体对。我研究的另一个目标是利用可卡因适配体形成链，在配体结合上组装。总之，我提出的研究将阐明功能性核酸是如何工作的，并将这些知识应用于新的应用。