RoL: EAGER: DESYN-C Spontaneously Synthesized RNA Protocells for Biological Catalysis

RoL：EAGER：DESYN-C 自发合成的 RNA 原始细胞用于生物催化

• 批准号: 1844119
• 负责人: Richard Zare
• 金额: $ 30万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844119&HistoricalAwards=false
• 关键词: RoL; EAGER; DESYN; Spontaneously; Synthesized

The core activity of a cell involves the high-fidelity replication of RNA and DNA. Protein synthesis is necessary to accomplish this objective. The variety of protein activities present leads to complex cell behavior. This variety is due in large part to external environmental forces. This project will attempt to create a precursor to a synthetic cell; a protocell. Think of this as a stepping stone between a vessel containing a mixture of chemicals and a fully-functional cell. The protocells will be micron-sized water droplets containing simple molecules. In such confined environments, spontaneous reactions have been observed to occur. This project, if successful, might help explain how life began, and facilitate the exploration of the catalytic functions of ribozymes.The project is an attempt to construct protocells from water microdroplets. The approach utilizes in situ synthesis of nucleotide, oligonucleotide, and phospholipids in aerosol microdroplets with geometric confinement and a heterogeneous air-water interface. The intellectual merits of the proposed research on synthesizing protocells and applications are: (1) How to form cellular membranes from simple phospholipid precursor molecules; (2) How to construct RNAs from ribose, nucleobase, metal and phosphoric acid; (3) How to build complex RNA molecules such as RNA oligomers, double-strand RNAs, ribozymes, and organometallic hybrid RNA enzymes; (4) How to utilize the protocell containing RNA ribozymes for catalysis, RNA editing, and switching biochemical reactions. The formation of oligomer products from the fluorescently tagged reactant nucleotides will be probed using fluorescence spectroscopy methods. Complete characterization of metabolic reactions and catalytic reactions using mass spectrometry will be achieved.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞的核心活动包括RNA和DNA的高保真复制。蛋白质合成是实现这一目标的必要条件。蛋白质活动的多样性导致了复杂的细胞行为。这种变化在很大程度上是由于外部环境的力量。这个项目将尝试创造一个合成细胞的前体；一个原始细胞。可以把它看作是一个包含化学物质混合物的容器和一个功能齐全的细胞之间的垫脚石。原始细胞将是含有简单分子的微米大小的水滴。在这样的密闭环境中，人们观察到自发反应的发生。这个项目，如果成功，可能有助于解释生命是如何开始的，并促进探索核酶的催化功能。该项目尝试用微水滴构建细胞原型。该方法利用核苷酸、寡核苷酸和磷脂在具有几何约束和非均相空气-水界面的气溶胶微滴中原位合成。拟研究的原细胞合成及其应用的智力优势在于：(1)如何从简单磷脂前体分子形成细胞膜；(2)如何利用核糖、核碱基、金属和磷酸构建rna；(3)如何构建RNA低聚物、双链RNA、核酶、有机金属杂交RNA酶等复杂RNA分子；(4)如何利用含有RNA核酶的原细胞进行催化、RNA编辑和开关生化反应。荧光标记的反应物核苷酸的低聚产物的形成将使用荧光光谱方法进行探测。完整的表征代谢反应和催化反应使用质谱将实现。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。