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

NSF/DMR-BSF：协同生物聚合物共组装调节合成网络中翻译和复制的出现

• 批准号: 2004846
• 负责人: David Lynn
• 金额: $ 52.5万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004846&HistoricalAwards=false
• 关键词: NSF; DMR; BSF; Synergistic; biopolymer

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.

第1部分。非技术摘要已被广泛概念化为一种计算，优化了信息的存储和使用以实现进化。在地球上，生命利用了聚合物的协调，将DNA中的“数字”信息存储与蛋白质的环境响应的“模拟”功能。这种协调是通过称为核糖体的分子信息流的数字到分析转换器（DAC）实现的。基于当前准备和修改聚合物的合成能力，该提案的目的是扩展生命中的共同聚合物网络以实现替代复制和合成翻译，从而将计算扩展到现有的生物聚合物之外。从概念上讲，实现这一目标将通过将可转化的材料移至生物聚合物之外，生成正交材料并与当前的生物学网络兼容，并揭示识别地球以外的生命的新机会，从而改变我们对宇宙生活的理解。实现这些目标有可能培训新一代物质科学家，自然地弥合合成，替代性和自然生物材料的世界，捕捉学者的想象力，并在这个星球和超越第2部分的跨越能源的范围内，在该星球上进行额外生物学外的化学进化应用。生物聚合物的共同组装以及允许表征复杂聚合物混合的合成和分析工具，现在可以探索协同驱动物理相变的反应 - 扩散聚合网络。这样的寡聚网络可以达到关键的旋律 - 捕捞阈值，以驱动液态液相分离。由此产生的富阶段创造了改变反应动力学的新反应环境。这种进行性张力，将动态物理阶段与改变的反应网络耦合，将用于创建自组织网络。随着富含固体的相通过Ostwald的阶段规则增长，潜水员订购了核的种群，从而在特定的粒径处访问液体固相变化，新相变得能够自体催化的传播，能够模拟新的聚合物生长。如果新聚合物经过设计以模板为初始组件，则将出现自催化反馈回路。该提案将比较两个系统以利用这种动态的物理/化学张力 - 共价连接的肽核酸嵌合体和单独的肽/核酸共组合，特别是在每个条件下，每个条件都会在对方的寡聚化中互互分子。这两种完整的翻译方法旨在建模最小的核糖体。这项工作将利用协作实验室中的协同和互补优势，即这些催化组装的必要结构和动力学分析。大自然的核糖体可实现单向聚合物的翻译，核酸为蛋白质。所提出的最小合成系统将是串联跨拟议低聚物的动态反应循环，并为定义将聚合物转换的一般规则定义为聚合物翻译提供了关键的原则证明。这种最小的系统方法最终有可能扩展到其他材料，以通过环境输入控制，以发展所需的功能。如果成功的话，这种方法将为分子计算和发现新型功能材料添加一个关键的新策略。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，认为通过评估被认为是宝贵的支持。

项目成果

Capturing Nested Information from Disordered Peptide Phases

从无序肽相中捕获嵌套信息

• DOI: 10.1002/pep2.24215
• 发表时间: 2021
• 期刊: Peptide science
• 影响因子: 2.4
• 作者: Gordon, Christella K;Luu, Regina;Lynn, David G
• 通讯作者: Lynn, David G

Liquid-like phases preorder peptides for assembly

类液相预排序肽进行组装

• DOI: 10.1002/syst.202000007
• 发表时间: 2020
• 期刊: ChemSystemsChem
• 作者: 2. Rengifo, Rolando F;Sementilli, Anthony;Kim, Youngsun;Liang, Chen;Li, Noel Xiang’An;Mehta, Anil K;Lynn, David G
• 通讯作者: Lynn, David G