Nonenzymatic RNA Replication

在化学系生命过程化学项目的支持下，杰克W。来自马萨诸塞州总医院和哈佛大学的绍斯塔克将研究与早期地球生命起源有关的生命前化学。拟议的工作将集中在原始RNA分子如何在没有酶的情况下复制。这项研究的重点是如何生命是一种自然现象，可以根据化学和物理定律出现。开展拟议的研究将有助于培养下一代的世纪科学家在化学和化学生物学领域。拟议的实验程序将使研究生和博士后研究员获得广泛的化学方法，包括有机合成，反应动力学，晶体学，质谱和NMR结构测定的专门培训。实验室的发现将传达给尽可能广泛的受众，以回应公众对生命起源的巨大兴趣以及宇宙其他地方可能存在生命的可能性。这一推广活动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。拟议的研究将推进益生元化学和RNA化学的知识。目标是了解化学能如何被收集并用于驱动复制，以及复杂RNA系统的紧急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研究生命在长序列（如病毒RNA基因组或细胞DNA基因组）的酶催化复制进化之前从非常复杂的小RNA片段混合物中出现的可能性。现代测序技术的使用将提供深入了解如何RNA复制和复制可以实现连续和准确。这个奖项反映了NSF的法定使命，并已被认为是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的支持。

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.