NSF/DMR-BSF: Synergistic biopolymer co-assembly regulating the emergence of translation and replication in synthetic networks

第一部分：非技术总结生活被广泛地概念化为优化信息存储和使用以实现进化的计算。在地球上，生命利用聚合物的协作性，将DNA中的“数字”信息存储与蛋白质对环境响应的“模拟”功能结合在一起。这种协作性是通过被称为核糖体的分子信息流的数模转换器(DAC)实现的。基于目前制备和修饰聚合物的合成能力，这一提议的目标是扩展生命的互惠聚合物网络，以实现替代复制和合成翻译，将计算扩展到现有生物聚合物之外。从概念上讲，实现这一目标将改变我们对宇宙中生命的理解，通过将可进化材料转移到生物聚合物之外，产生与当前生物网络垂直且兼容的功能材料，并揭示识别地球以外生命的新机会。实现这些目标有可能培养新一代材料科学家和学者，他们自然地连接合成生物材料、替代生物材料和天然生物材料的世界，激发学者和公众的想象力，使其在地球上和以外的现有生物学之外的化学进化方面具有潜在的应用。第二部分技术概述建立在嵌段共聚物和聚合物共混物的实际成功、生物聚合物自组装和共聚的新兴能量代码以及允许表征复杂聚合物混合物的合成和分析工具的基础上，现在可以探索协同驱动物理相变的反应-扩散聚合网络。这种齐聚网络可以达到推动液-液相分离的关键Flory-Huggins阈值。由此产生的富含溶质的相创造了改变反应动力学的新的反应环境。这种渐进的张力，将动态的物理相与改变的反应网络相结合，将被用来创建自组织网络。当富含溶质的相通过Ostwald的阶段规则增长时，播撒着不同有序的核群体，这些核在特定的颗粒尺寸下访问液-固相的变化，新相变得能够自动催化生长能够模板新的聚合物生长的准晶表面。如果将新聚合物设计为初始组装的模板，则会出现自动催化反馈回路。这项提议将比较两个系统，以利用这种动态的物理/化学紧张--共价连接的肽-核酸嵌合体和分离的肽/核酸共同组装，特别是在每个模板彼此分子间齐聚的条件下。这两种互补的翻译方法旨在模拟最小的核糖体。这项工作将利用合作实验室中的协同和互补优势，以及对这些催化组件进行必要的结构和动力学分析。自然界的核糖体实现了单向的聚合物翻译，将核酸转化为蛋白质。所提出的最小合成系统将是催化交叉模板齐聚物动态反应循环的凝聚体，并为定义限制聚合物到聚合物翻译的一般规则提供关键的原则证明。这种最小系统方法最终有可能扩展到其他材料，以进化受环境输入控制的所需功能。如果成功，这种方法将为分子计算和发现新的功能材料增加一个关键的新战略。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Part 1. Non-Technical SummaryLife has been broadly conceptualized as a computation optimizing the storage and use of information to enable evolution. On Earth, life exploits polymer cooperativity, coupling “digital” information storage in DNA with an environmentally responsive “analog” function of proteins. Such cooperativity is achieved through the digital-to-analog converter (DAC) of molecular information flow known as the ribosome. Based on current synthetic capabilities for preparing and modifying polymers, the goal of this proposal is to extend life’s mutualistic polymer networks to achieve alternative replication and synthetic translation, extending the computations beyond existing biopolymers. Conceptually, achieving this goal would change our understanding of life in the Universe by moving evolvable materials beyond biopolymers, generating functional materials both orthogonal to and compatible with current biological networks, and revealing new opportunities for identifying life beyond Earth. Achieving these goals have the potential to train a new generation of material scientists, scholars who naturally bridge the worlds of synthetic, alternative, and natural biomaterials, capturing the imagination of scholars and the lay public with the potential applications for chemical evolution outside of extant biology on this planet and beyond.Part 2. Technical SummaryBuilding on the practical success of block copolymers and polymer blends, the emerging energetic codes for self- and co-assembly of biopolymers, and the synthetic and analytical tools allowing for the characterization of mixtures of complex polymers, it now becomes possible to explore reaction-diffusion polymerization networks that cooperatively drive physical phase changes. Such oligomerization networks can reach critical Flory-Huggins thresholds to drive liquid-liquid phase separation. The resulting solute rich phases create new reaction environments that change reaction kinetics. This progressive tension, coupling dynamic physical phases with altered reaction networks, will be used to create self-organizing networks. As the solute-rich phases grow via Ostwald’s rule of stages, seeding diverse ordered populations of nuclei that access liquid-solid phase changes at specific particle sizes, the new phase becomes capable of autocatalytic propagation of a paracrystalline surface able to template new polymer growth. An autocatalytic feedback loop will appear if the new polymer is engineered to template the initial assembly. This proposal will compare two systems to exploit this dynamic physical/chemical tension -- a covalently connected peptide-nucleic acid chimera and separate peptide/nucleic acid co-assemblies, specifically under conditions where each templates the other’s oligomerization intermolecularly. These two complementary approaches to translation are designed to model a minimal ribosome. The work will take advantage of the synergistic and complementary strengths in the collaborating laboratories, the necessary structural and kinetic analyses of these catalytic assemblies. Nature’s ribosome achieves unidirectional polymer translation, nucleic acid to protein. The proposed minimal synthetic system will be a coacervate catalyzing dynamic reaction cycles of cross-templating oligomers and provide a critical proof-of-principle for defining the general rules limiting polymer to polymer translation. This minimal system approach has the potential ultimately to extend to other materials for evolving desired function as controlled by environmental inputs. If successful, this approach will add a critical new strategy for molecular computing and discovering novel functional materials.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.