Collaborative Research: Supramolecular Materials by Nucleic Acid Block Copolymer Self-Assembly

合作研究：核酸嵌段共聚物自组装超分子材料

• 批准号: 1411126
• 负责人: Stefan Zauscher
• 金额: $ 39万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1411126&HistoricalAwards=false
• 关键词: Collaborative; Research; Supramolecular; Materials; Nucleic

Nontechnical: These Collaborative awards by the Biomaterials program in the Division of Materials Research to Duke University (Lead) and North Carolina State University (Nonlead) are cofunded by the Biomedical Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems (ENG). These awards are for the enzymatic synthesis of long DNA chains and the systematic scientific approaches for exploring their assembly into aggregates (micelles) and networks, and are expected to advance the field of DNA-based materials. The proposed research is transformative because it will provide design rules for the synthesis of multi-functional DNA chains that can self-assemble into morphologies with potential for drug delivery applications. The proposed research will also yield methods and strategies to fabricate oriented DNA nanowire networks over large areas. These polynucleotide networks can be metallized and thus contribute to an essential need in the rapidly growing number of nanoscale devices with applications ranging from flexible electronics to photovoltaics. The proposed projects are also emblematic for a research and training paradigm termed Reverse Engineering Biology (REBio), where students will integrate biological sciences within the engineering paradigm of design to forward engineer new products and processes. Under the REBio paradigm, the PIs are committed to: (i) providing an integrated educational and research training program for undergraduate and graduate students involved with the project; and (ii) increasing public awareness and engagement with some of the scientific concepts underlying the proposed research through hands-on, informal education opportunities for K-12 students and general audiences.Technical: Polyelectrolyte block-co-polymers show rich micellization behavior in solution and hold promise for novel functional materials in nano- and biotechnological applications. To date, however, the synthesis of polynucleotides with high molecular weight, and of oligonucleotide hybrid block-copolymers is still a challenge. Moreover, little is known about the design rules for micellar morphologies formed by block-co-polynucleotides. Despite the astounding successes in the field of DNA nanotechnology, the alignment, patterning and large scale ordering of polynucleotide assemblies on surfaces are still challenging problems that prevent use of these materials in functional devices. The research activities in this interdisciplinary, collaborative research proposal address these shortcomings. The research team will combine theory, experiment and simulations to answer questions in three specific aims: (1) to provide guidelines for synthesis and self-assembly of block-co-polynucleotides into a range of micellar structures in aqueous solutions; (2) to develop fundamental understanding and control over the assembly of functional nucleic acid networks on surfaces and the use of the networks as scaffolds for metallization; and (3) to provide cost-effective access to terminal deoxynucleotidyl Transferase needed for the scale-up of polynucleotide materials synthesis.

非技术性：这些由材料研究部生物材料项目授予杜克大学（牵头）和北卡罗来纳州州立大学（非牵头）的合作奖项由化学、生物工程、环境和运输系统部（ENG）的生物医学工程项目共同资助。这些奖项是为了表彰长DNA链的酶促合成以及探索其组装成聚集体（胶束）和网络的系统科学方法，并有望推动DNA基材料领域的发展。拟议的研究是变革性的，因为它将为多功能DNA链的合成提供设计规则，这些DNA链可以自组装成具有药物递送应用潜力的形态。拟议的研究还将产生在大面积上制造定向DNA纳米线网络的方法和策略。这些多核苷酸网络可以被金属化，从而有助于快速增长的纳米级器件的基本需求，其应用范围从柔性电子到光电子学。拟议的项目也是一个研究和培训范式的象征，称为逆向工程生物学（REBio），学生将在设计的工程范式中整合生物科学，以推进工程新产品和工艺。在REBio范式下，PI致力于：（i）为参与该项目的本科生和研究生提供综合教育和研究培训计划;（ii）通过为K-12学生和普通观众提供实践和非正式教育机会，提高公众对拟议研究中的一些科学概念的认识和参与。聚电解质嵌段共聚物在溶液中表现出丰富的胶束化行为，在纳米和生物技术应用中有望成为新型功能材料。然而，迄今为止，具有高分子量的多核苷酸和寡核苷酸杂合嵌段共聚物的合成仍然是一个挑战。此外，鲜为人知的是，由嵌段共多核苷酸形成的胶束形态的设计规则。尽管DNA纳米技术领域取得了惊人的成功，但表面上多核苷酸组装体的对齐、图案化和大规模有序化仍然是阻碍这些材料在功能器件中使用的挑战性问题。在这个跨学科的研究活动，合作研究建议解决这些缺点。该研究小组将联合收割机理论、实验和模拟相结合，回答三个具体目标的问题：（1）为嵌段多核苷酸在水溶液中合成和自组装成一系列胶束结构提供指导;（2）对功能性核酸网络在表面上的组装和使用网络作为金属化支架的基本理解和控制;和（3）提供成本有效地获得放大多核苷酸材料合成所需的末端脱氧核苷酸转移酶。