INSPIRE Track 1: Origins-of-life and self-evolving polymeric materials

该INSPIRE奖部分由生物科学理事会分子和细胞生物科学部的分子生物物理学小组资助;物理学系生命系统物理学项目，以及数学和物理科学理事会化学部的生命过程化学计划。这个INSPIRE项目的目标是了解益生元的最早步骤，进化一个长期存在的重大挑战问题是生命系统如何从物理化学相互作用中产生。化学是如何变成生物学的？什么时候，无方向的化学反应开始利用健康，变得自私，开始与他人竞争，并经历达尔文进化？ 如果成功，这个项目将提供一个合理的假设，随机链序列如何导致信息传输链，因为化学成为生物学，并可能成为新的聚合物材料，不仅是自组织的，而且实际上是自我进化的。 将采用理论与实验相结合的方法来实施这一具有挑战性和风险性的项目。这是一个潜在的变革性项目，因为很少有人了解序列特异性聚合物，如蛋白质和类肽折叠体，如何通过随机过程从随机单体序列中产生。生命如何从化学中产生的问题是科学中最引人注目和最悠久的问题之一。关于RNA世界、膜世界中生命的起源，人们已经提出了很多假设，比如代谢优先或代码优先机制，但很少有人关注达尔文主义的自私类生物行为是如何从非达尔文主义的化学中产生的这一核心问题。这是一个长期存在的基本问题，这个项目是高风险的，因为它是在生命起源领域的性质，任何特定的机制提出的生命起源从化学将受到怀疑。在聚合物序列空间中识别功能结构域的复杂性是如此巨大，理论和实验必须非常紧密地合作来解决这个问题。 实验性地解决这个问题的工具只是最近才被开发出来。聚合物合成的进展第一次达到了令人兴奋的地步：现在可以合成精确控制单体序列和长度的非天然聚合物，并将这些链组装成蛋白质样结构。这种能力使人们能够测试关于聚合物链中的信息含量如何影响其结构和功能的最基本问题。

This INSPIRE award is partially funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences; the Physics of Living Systems Program in the Division of Physics, and the Chemistry of Life Processes Program in the Division of Chemistry in the Directorate of Mathematical and Physical Sciences.The objective of this INSPIRE project is to understand the earliest steps in prebiotic evolution. A longstanding grand-challenge question is how living systems arose from physico-chemical interactions. How did chemistry become biology? When did undirected chemical reactions begin to capitalize on fitness, become self-serving, start competing with others, and undergo Darwinian evolution? If successful, this project will provide a plausible hypothesis for how random chain sequences could have led to information-transmitting chains, as chemistry becomes biology and potentially to new polymeric materials that are not just self-organizing, but are actually self-evolving. An integrated approach of theory and experiment will be used to carry out this challenging and risky project. This is a potentially transformative project because very little is understood about how sequence-specific polymers, such as proteins and peptoid foldamers, could arise through stochastic processes from random monomer sequences. Questions of how life arose from chemistry are among the most compelling and longstanding in science. Much has been hypothesized about origins of life in the RNA world, membrane world, by metabolism-first or code-first mechanisms, for example, but very little of this discussion focuses on the central question of how Darwinian self-serving bio-like behavior arose from non-Darwinian chemistry. This is a long-standing fundamental question and this project is high-risk because it is in the nature of the origins-of-life field that any particular mechanism proposed for the origin of life from chemistry will be met with skepticism. The complexity of identifying functional domains in polymer sequence space is so vast, both theory and experiment must work very closely together to address this problem. The tools to approach this problem experimentally have only just recently been developed. Advances in polymer synthesis have reached an exciting point for the first time: one can now synthesize non-natural polymers with exact control of monomer sequence and length, and assemble these chains into protein-like architectures. This capability allows one to test the most fundamental questions about how information content in polymer chains impacts their structure and function.