Nonenzymatic RNA Replication

非酶RNA复制

• 批准号: 2104708
• 负责人: Jack Szostak
• 金额: $ 100万
• 依托单位: Massachusetts General Hospital
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2104708&HistoricalAwards=false
• 关键词: Nonenzymatic; RNA; Replication

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Professor Jack W. Szostak from the Massachusetts General Hospital and Harvard University will study prebiotic chemistry relevant for the origin of life on the early Earth. The proposed work will focus on how primordial RNA molecules could have replicated without enzymes. This research focuses on how life is a natural phenomenon that can emerge according to the laws of chemistry and physics. Carrying out the proposed research will contribute to training the next generation of 21st century scientists in the fields of chemistry and chemical biology. The proposed experimental procedures will allow graduate students and postdoctoral fellows to acquire specialized training in a broad range of chemical methods including organic synthesis, reaction kinetics, structure determination by crystallography, mass spectrometry and NMR. The laboratory’s findings will be communicated to the broadest possible audience in response to the enormous public interest in the origin of life and the possibility that life may exist elsewhere in the Universe. This outreach will both engage and educate non-scientists in the value and power of evidence-based thinking. A broader appreciation of and respect for science would be an enormous societal benefit. The proposed research will advance knowledge of prebiotic chemistry and the chemistry of RNA. The objectives are to understand how chemical energy could be harvested and used to drive replication, and the emergent behaviors of complex RNA systems that will lead to non-enzymatic replication. The experiments related to activation chemistry will explore how high-energy compounds resulting from exposure to UV light can drive the chemical activation of nucleotides and thus the non-enzymatic replication of RNA. The exploration of a new model for RNA replication will examine the possibility that life emerged from a very complex mixture of small RNA fragments, prior to the evolution of enzyme-catalyzed replication of long sequences such as viral RNA genomes or cellular DNA genomes. The use of modern sequencing technology will provide insight into how RNA copying and replication can be achieved continuously and accurately.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.

在化学系生命过程化学项目的支持下，来自马萨诸塞州总医院和哈佛大学的 Jack W. Szostak 教授将研究与早期地球生命起源相关的生命前化学。拟议的工作将集中于原始 RNA 分子如何在没有酶的情况下复制。这项研究的重点是生命如何成为一种根据化学和物理定律出现的自然现象。开展拟议的研究将有助于培养化学和化学生物学领域的下一代 21 世纪科学家。拟议的实验程序将使研究生和博士后研究员获得广泛化学方法的专门培训，包括有机合成、反应动力学、晶体学结构测定、质谱和核磁共振。该实验室的研究结果将传达给尽可能广泛的受众，以回应公众对生命起源以及生命可能存在于宇宙其他地方的可能性的巨大兴趣。这种推广活动将吸引非科学家并教育他们了解循证思维的价值和力量。对科学更广泛的认识和尊重将带来巨大的社会效益。拟议的研究将增进对生命起源前化学和 RNA 化学的了解。目标是了解如何收集化学能并用于驱动复制，以及复杂 RNA 系统的新兴行为将导致非酶复制。与活化化学相关的实验将探索暴露于紫外线下产生的高能化合物如何驱动核苷酸的化学活化，从而驱动 RNA 的非酶复制。对 RNA 复制新模型的探索将检验生命从非常复杂的小 RNA 片段混合物中出现的可能性，然后再进化出病毒 RNA 基因组或细胞 DNA 基因组等长序列的酶催化复制。现代测序技术的使用将深入了解如何连续、准确地实现 RNA 复制和复制。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。