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.

细胞的核心活动涉及RNA和DNA的高保真复制。蛋白质合成是实现这一目标所必需的。存在的蛋白质活性的多样性导致复杂的细胞行为。这种变化在很大程度上是由于外部环境的力量。这个项目将试图创造一个合成细胞的前体;一个原始细胞。可以把它想象成一个垫脚石，在一个含有化学物质混合物的容器和一个功能齐全的细胞之间。原始细胞将是含有简单分子的微米大小的水滴。在这种封闭的环境中，已经观察到自发反应发生。这个项目如果成功的话，可能有助于解释生命是如何开始的，并促进对核酶催化功能的探索。该方法利用原位合成的核苷酸，寡核苷酸和磷脂的气溶胶微滴的几何限制和异质性的空气-水界面。本文提出的合成原始细胞及其应用研究的智力价值是：（1）如何从简单的磷脂前体分子形成细胞膜;（2）如何从核糖、核碱基、金属和磷酸构建RNA;（3）如何构建复杂的RNA分子，如RNA寡聚体、双链RNA、核酶和金属有机杂交RNA酶;（4）如何利用含有RNA核酶的原始细胞进行催化、RNA编辑和转换生化反应。将使用荧光光谱法探测来自荧光标记的反应物核苷酸的寡聚体产物的形成。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。