CAREER: Programming Dynamic Growth and Reconfiguration in Nucleic Acid Nanomaterials

职业：核酸纳米材料动态生长和重构的编程

• 批准号: 1450747
• 负责人: Elisa Franco
• 金额: $ 50.04万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1450747&HistoricalAwards=false
• 关键词: CAREER; Programming; Dynamic; Growth; Reconfiguration

Non-technical: This CAREER Award by the Biomaterials program in the Division of Materials Research to the University of California, Riverside will be used to develop responsive, programmable materials made with RNA and synthetic genes. Biological organisms control their shape in space and time by producing and directing the assembly of molecular building blocks with molecular circuits. The cellular scaffold, for instance, grows and reorganizes its shape in response to environmental stimuli that trigger the production of the scaffold materials and the molecules that regulate its organization. Reproducing the properties of cellular scaffolds in synthetic materials will advance our ability to manipulate matter at the nanoscale and create reconfigurable, regenerating materials. However, cellular materials are too complex to be directly embedded in a man-made material, and chemical synthesis of active assembling materials is very laborious. In contrast, DNA and RNA are highly programmable polymers that can be used to build self-assembling structures as well as molecular control circuits. The overall objective of this project is to couple RNA structures and circuits to build dynamic RNA nanomaterials encoded in minimal artificial DNA gene networks; experiments and modeling will be combined to achieve this objective. RNA nanostructures will be assembled from monomers (tiles) produced by artificial genes. Timed assembly and disassembly instructions will also be encoded in RNA signals generated by synthetic gene networks, resulting in a new generation of smart materials capable of growth, metamorphosis, and self-repair. This grant will support graduate and undergraduate students to perform cutting edge research in biomaterials science. The PI and her team of students will also collaborate with the University of California Television (UCTV), and the UC Riverside Media Relations office to produce short educational clips to be aired on UCTV.Technical: This research project aims at building active, programmable nucleic acid biomaterials encoded in synthetic genes. Modular RNA nanostructures (tubes and ribbons) will be designed to self-assemble from monomers (tiles) and grow, self-regulate and repair. Production and control pathways will be embedded in transcriptional circuits and only involve DNA, RNA and off-the-shelf proteins. Mathematical models will elucidate design principles and guide experiments. This research has the potential to transform current methods to design and build synthetic materials, because these RNA dynamic nanostructures will be produced, self-assembled, and regulated from a finite number of components, rather than being synthesized with a top-down approach. This approach mimics the organization of cellular pathways for the synthesis and control of molecular materials such as the cytoskeleton: however, our materials will be rationally designed and built, exploiting the programmability of nucleic acids. This project is integrated with an outreach program aimed at disseminating research results and at inspiring high school and undergraduate students to pursue higher education through the production of educational materials and short video clips in collaboration with the University of California Television (UCTV), and the UC Riverside Media Relations office.

非技术：由加州大学河滨分校材料研究部生物材料项目颁发的职业奖将用于开发由RNA和合成基因制成的反应性、可编程材料。生物有机体通过产生和指挥带有分子电路的分子构件的组装来控制它们在空间和时间上的形状。例如，细胞支架在环境刺激下生长并重组其形状，从而触发支架材料和调节其组织的分子的产生。在合成材料中再现细胞支架的特性，将提高我们在纳米尺度上操纵物质的能力，并创造可重构、可再生的材料。然而，细胞材料过于复杂，无法直接嵌入人造材料中，而化学合成活性组装材料非常费力。相比之下，DNA和RNA是高度可编程的聚合物，可用于构建自组装结构以及分子控制电路。该项目的总体目标是将RNA结构和电路偶联，以构建在最小人工DNA基因网络中编码的动态RNA纳米材料；实验和建模将结合起来实现这一目标。RNA纳米结构将由人工基因产生的单体组装而成。定时组装和拆卸指令也将被编码在合成基因网络产生的RNA信号中，从而产生能够生长、变形和自我修复的新一代智能材料。这项资助将支持研究生和本科生在生物材料科学领域进行前沿研究。PI和她的学生团队还将与加州大学电视台（UCTV）以及加州大学河滨分校媒体关系办公室合作，制作在UCTV上播出的教育短片。技术：本研究项目旨在构建合成基因编码的活性可编程核酸生物材料。模块化RNA纳米结构（管状和带状）将被设计成从单体（瓦片）自组装并生长、自我调节和修复。生产和控制途径将嵌入转录回路中，只涉及DNA、RNA和现成的蛋白质。数学模型将阐明设计原理和指导实验。这项研究有可能改变目前设计和制造合成材料的方法，因为这些RNA动态纳米结构将由有限数量的组分产生、自组装和调节，而不是用自上而下的方法合成。这种方法模拟了合成和控制分子材料（如细胞骨架）的细胞途径的组织：然而，我们的材料将被合理地设计和构建，利用核酸的可编程性。该项目整合了一个旨在传播研究成果的外展计划，并与加州大学电视台（UCTV）和加州大学河滨分校媒体关系办公室合作，通过制作教育材料和短视频片段，激励高中生和本科生接受高等教育。