Nonenzymatic RNA Replication

在化学学部生命过程化学项目的支持下，来自麻省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益生元化学。拟议的工作将集中在原始RNA分子如何在没有酶的情况下进行复制。这项研究的重点是生命是如何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21世纪化学和化学生物学领域的下一代科学家。拟议的实验程序将允许研究生和博士后获得广泛的化学方法的专门培训，包括有机合成、反应动力学、晶体学、质谱和核磁共振结构测定。为了回应公众对生命起源的巨大兴趣以及宇宙中其他地方可能存在生命的可能性，实验室的发现将传达给尽可能广泛的受众。这种拓展将吸引和教育非科学家了解循证思维的价值和力量。更广泛地欣赏和尊重科学将带来巨大的社会效益。这项研究将促进对益生元化学和RNA化学的认识。目标是了解如何收集和使用化学能来驱动复制，以及复杂RNA系统的紧急行为，这些行为将导致非酶复制。与激活化学相关的实验将探索暴露在紫外线下产生的高能化合物如何驱动核苷酸的化学激活，从而推动RNA的非酶复制。对RNA复制新模型的探索将检验生命出现于小RNA片段非常复杂的混合物的可能性，在酶催化的长序列复制（如病毒RNA基因组或细胞DNA基因组）进化之前。现代测序技术的使用将为RNA复制和复制如何连续准确地实现提供见解。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。

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.