Liquid Crystals of Nanonucleic Acids: Hierarchical Self-Assembly as a Route to Prebiotic Selection, Templating, and Autocatalysis

纳米核酸液晶：分层自组装作为益生元选择、模板化和自催化的途径

• 批准号: 1611272
• 负责人: Noel Clark
• 金额: $ 42万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1611272&HistoricalAwards=false
• 关键词: Liquid; Crystals; Nanonucleic; Acids; Hierarchical

Non-technical: This award by the Biomaterials program in the Division of Materials Research to the University of Colorado Boulder is to develop a chemical process, which is referred to in the proposal as "liquid crystal autocatalysis." This project explores as the mechanism for the appearance of nucleic acids in the prebiotic era. This proposal is expected to develop the understanding on how a "Liquid Crystal (LC) World" preceded the nucleic acid world by providing its basic molecular design and feedstock. Within the liquid crystal phase, duplex-forming nano-nucleic acids are held in end-to-end contact to a structure that catalytically promotes their chemical ligation, and this forms the basis for an autocatalytic feedback loop. The outcomes from these studies could have potential in offering new tools for in situ synthesis of nucleic acid-based nanotechnology, and potentially leading to a whole new platform for nano-controlled nucleic acid, and assembly/disassembly of nucleic acids for different applications such as drug/gene delivery, bioderived motors, etc. The proposed educational broader impact activities will help to inspire high school students in STEM, and would provide valuable undergraduate research opportunities. Technical: The proposed research program will be focusing on exploring the features of this ancient Liquid Crystal (LC) World and especially its capacity for providing the molecular feedstock for the nucleic acids (NAs) world. The research will diversify the input chemical stock for starting the LC World by exploring liquid crystal autocatalysis under successively more primitive and diverse initial conditions, beginning with ultra-short duplexing NAs down to single bases, and evolving to mixtures of homologs made with proposed prebiotic synthetic or chemical degradation schemes, with the goal of understanding the robustness of liquid crystal autocatalysis in the presence of chemical noise. This award will develop the ability of liquid crystal autocatalysis to narrow molecular diversity to generate homogeneous polymer populations such as the nucleic acids. This project will also explore the potential of the LC World for producing nucleic acids with chemically and catalytically active secondary structures, by feeding liquid crystal autocatalytic systems with mixtures of nanonucleic acids that incorporate randomness in sequence and lengths. This approach will enable development of strategies for making chains capable of adopting a secondary structure. This project will investigate the evolution of nucleic acid populations starting under varying conditions of randomness in thermal cycling and ligation, searching for specific subpopulations of sequences or folding motifs. Finally, new strategies will be explored for catalytic ligation and chemical stabilization of self-assembled DNA. This path has definite potential for technological novelty, offering new tools for in situ synthesis in the hugely expanding field of NA-based nanotechnology, and potentially leading to a whole new platform for nano-controlled NA chemistry.

非技术性：科罗拉多博尔德大学材料研究部生物材料项目授予科罗拉多博尔德大学的这一奖项是为了开发一种化学工艺，在提案中被称为“液晶自催化”。这个项目探索的是益生菌时代核酸出现的机制。这项提议预计将通过提供基本的分子设计和原料，加深对“液晶世界”如何领先于核酸世界的理解。在液晶相中，形成双链的纳米核酸与催化促进其化学连接的结构保持端到端的接触，这形成了自催化反馈循环的基础。这些研究的结果可能会为原位合成基于核酸的纳米技术提供新的工具，并可能导致一个全新的纳米控制核酸平台，以及不同应用领域的核酸组装/拆解，如药物/基因输送、生物衍生马达等。拟议的更广泛的教育影响活动将有助于激励高中生学习STEM，并将提供宝贵的本科生研究机会。技术：拟议的研究计划将集中于探索这个古老的液晶(LC)世界的特征，特别是它为核酸(Nas)世界提供分子原料的能力。这项研究将通过在更原始和更多样化的初始条件下探索液晶自催化来使启动LC World的输入化学物质多样化，从超短双链到单碱基，再到通过建议的益生菌合成或化学降解方案形成的同系物的混合物，目的是了解液晶自催化在存在化学噪声的情况下的稳健性。该奖项将发展液晶自催化的能力，以缩小分子多样性，以产生均一的聚合物群体，如核酸。该项目还将探索LC World生产具有化学和催化活性二级结构的核酸的潜力，方法是向液晶自催化系统提供在序列和长度上包含随机性的纳米核酸混合物。这种方法将有助于制定战略，使链能够采用二级结构。这个项目将研究在热循环和连接的不同随机性条件下开始的核酸种群的进化，寻找序列或折叠基序的特定亚群。最后，将探索催化连接和化学稳定自组装DNA的新策略。这条道路具有一定的技术新颖性潜力，为基于NA的纳米技术领域的巨大扩展提供了新的原位合成工具，并可能导致一个全新的纳米控制NA化学平台。