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.
