NSF/DMR-BSF: Supramolecular mutualism in Functional Nucleic acid and Peptide Co-assemblies

NSF/DMR-BSF：功能性核酸和肽共组装体中的超分子互利共生

• 批准号: 1610377
• 负责人: David Lynn
• 金额: $ 45万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1610377&HistoricalAwards=false
• 关键词: NSF; DMR; BSF; Supramolecular; mutualism

Non-technical: This NSF/BSF award by the Biomaterials program in the Division of Materials Research to Emory University is a study in understanding the emergence of chemical evolution for the design and preparation of biomimetic systems as complex as artificial cells and tissues. This award is co-funded by the following programs: 1) BMAT program in the Division of Materials Research; 2) Catalysis and Biocatalysis program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG); and 3) Global Venture Funds in the Office of International Science and Engineering. This collaborative research combines complementary expertise of scientists in US and Israel. While man-made processes and products are typically passive and static, those found in the living world are active and dynamic. To better understand this dynamic, active and complex system, this project will use radically different approaches in areas ranging from materials sciences in the design and study of complex systems for the construction of self-organizing, multi-component chemical networks for storage and amplification of molecular-scale information. This award will design bottom-up synthesis of novel mesoscale assemblies, which in turn will be used to build cooperative interactions between different biopolymer families to achieve the first synthetic mutualistic network for materials research. These studies are expected to result in new materials benefiting biotechnology in diagnostics, gene delivery, drug delivery, etc. As part of this project, new core chemistry classes that blend chemistry, polymers, and materials will be implemented to enhance educational curiosity in supramolecular mutualism. Mesoscale assemblies will be captured in simulations, visually building from blends and block polymers to mutualistic biopolymer networks. Videos will also be developed highlighting the sciences, the humor and the culture of the US and Israeli faculty and students. This project will also be developing novel teaching methods and interdisciplinary materials projects in the newly opened research/learning center - Science Commons - at Emory University. Technical: This collaborative research is focused on designing peptide/nucleic acids based dynamic and active assemblies that can catalyze their own replication. Toward this goal, the project will explore dynamic networks in regulating molecular evolution by: 1) elucidating the structure of nucleic acid/peptide intermolecular and nucleic acid/peptide conjugate assemblies; 2) studying their assembly pathways and defining control factors for assembly (pH, temperature and salt concentration); and 3) characterizing the mutualistic functions enabled by these assemblies and co-assemblies. The proposed iterative structural and functional analyses of these composites are expected to provide sufficient insight in constructing a synthetic digital-to-analog converter with alternative nucleic acid/peptide assemblies. The wealth of information developed on protein and nucleic acid interactions and the structural information that will be provided by these assemblies would allow one to engineer mutualistic behaviors, where cooperative peptide templates would serve as nucleic acid polymerases, and nucleic acid/peptide co-assemblies in catalyzing their own replication. These studies could be the first step in expanding and understanding the supramolecular assembly into self-organizing networks for novel materials. Just as the emergence of the ribosome provided a critical Darwinian threshold for our biosphere, one may see these studies as first set in demonstrating the use of mutualistic polymers and supramolecular catalysts for the creation of intelligent materials. This work is also expected to expand the analytic and modeling methods available for dynamic chemical systems, and for the cross catalytic networks that will serve as a foundation for a synthetic biology, which in turn will ultimately lead to evolutionary strategies for the discovery and optimization of functional materials.

非技术：这项由埃默里大学材料研究部生物材料项目颁发的NSF/BSF奖是一项研究，旨在理解化学进化的出现，以设计和制备像人工细胞和组织一样复杂的仿生系统。该奖项由以下项目共同资助：1)材料研究部BMAT项目；2)化学和生物工程，环境和运输系统（ENG）部门的催化和生物催化计划；3)国际科学与工程办公室的全球风险基金。这项合作研究结合了美国和以色列科学家的互补专业知识。虽然人造过程和产品通常是被动和静态的，但在生活世界中发现的过程和产品是主动和动态的。为了更好地理解这个动态的、活跃的和复杂的系统，该项目将在材料科学领域使用完全不同的方法，设计和研究复杂系统，以构建自组织的、多组分的化学网络，以存储和放大分子尺度的信息。该奖项将设计新型中尺度组件的自下而上合成，这反过来将用于建立不同生物聚合物家族之间的合作相互作用，以实现材料研究的第一个合成互惠网络。这些研究有望在诊断、基因传递、药物传递等方面产生有利于生物技术的新材料。作为该项目的一部分，新的核心化学课程将融合化学、聚合物和材料，以提高对超分子相互作用的教育好奇心。中尺度组装将在模拟中捕获，从混合物和嵌段聚合物到共生生物聚合物网络的视觉构建。还将制作视频，突出美国和以色列教师和学生的科学、幽默和文化。该项目还将在埃默里大学新开设的研究/学习中心-科学共享中心开发新的教学方法和跨学科材料项目。技术：这项合作研究的重点是设计基于肽/核酸的动态和活性组装，可以催化它们自己的复制。为了实现这一目标，该项目将通过以下方式探索调节分子进化的动态网络：1)阐明核酸/肽分子间和核酸/肽偶联物的结构；2)研究它们的组装途径，确定组装的控制因素（pH、温度和盐浓度）；3)表征这些组合和协同组合所实现的互惠功能。这些复合材料的迭代结构和功能分析有望为构建具有替代核酸/肽组件的合成数模转换器提供足够的见解。关于蛋白质和核酸相互作用的丰富信息以及这些组装将提供的结构信息将允许人们设计互惠行为，其中合作肽模板将作为核酸聚合酶，核酸/肽共组装在催化其自身复制中。这些研究可能是将超分子组装扩展和理解为新材料自组织网络的第一步。正如核糖体的出现为我们的生物圈提供了一个关键的达尔文阈值一样，人们可以将这些研究视为首次证明使用互惠聚合物和超分子催化剂来创造智能材料。这项工作也有望扩展动态化学系统和交叉催化网络的分析和建模方法，这些网络将作为合成生物学的基础，而合成生物学最终将导致发现和优化功能材料的进化策略。