NSF Center for Genetically Encoded Materials

NSF 基因编码材料中心

• 批准号: 2002182
• 负责人: Alanna Schepartz
• 金额: $ 2000万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2002182&HistoricalAwards=false
• 关键词: NSF; Center; Genetically; Encoded; Materials

The Center for Genetically Encoded Materials (C-GEM) develops new biologically-inspired methods to precisely tailor and build polymers. Polymers, which are comprised of repeated molecular units bonded together, are ubiquitous, from plastic products to DNA. By controlling the identity and linkages of the molecular units, the properties of polymers can be finely tuned, which has led to an explosion of new products and applications. Despite these advances, it is still extremely difficult to systematically and precisely control the sequence of the molecular units in a polymer. With this level of control, new polymers could be developed for information storage, textiles and fabrics, nano-sensors, and drug discovery and delivery. To accomplish this tough but transformative chemistry, C-GEM Is adapting two complementary approaches. First, C-GEM is re-engineering the ribosome to build bonds between molecules in sequence, much like natural ribosomes build proteins by assembling alpha-amino acids in sequence. Second, C-GEM is purposefully expanding the structures of natural polypeptides in ways that dramatically increase their chemical diversity and function. C-GEM also engages and trains diverse groups of students and postdoctoral researchers in collaborative teams at a rich new interface of chemistry, biology, and materials science. C-GEM also engages citizen scientists with a scientific discovery game, EteRNA, that introduces interested gamers to the key concepts of RNA structure, stability, and function. New EteRNA Challenges focus on the chemistry of the ribosome. Overall, C-GEM is establishing a future of bespoke polymers to address health, environmental, and industrial challenges, fostering innovation, and training a diverse workforce at multiple chemistry-biology-materials frontiers.C-GEM’s Phase II research plan includes interrelated goals that will expand ribosome-mediated chemistry to generate molecular architectures unique in both structure and function. C-GEM is also pursuing a parallel path in which innovative “late-stage functionalization” reactions convert ribosome-derived products into substances beyond the reach of extant biosynthesis. Novel and versatile tools to design, evolve, and characterize the molecules of translation will expand their chemical capacity in vitro and in vivo. C-GEM will also use new and existing technologies to determine the structures of the genetically encoded product molecules and polymers, as well as the mechanisms by which they are assembled. A suite of computational methods will evaluate, model, and predict the chemical capacity of wild type and engineered ribosomes, their translation factors, and the properties of the polymers they produce, signaling a new era in computational biomaterial design. Our goals also include strategies to prepare sequence-defined chemical polymers in useful quantities, enabling functions that impact biotechnology, in vivo imaging, molecular medicine, materials science, and drug delivery. A diverse set of education and participation programs integrates research with training, establishes a diverse chemical workforce, and engages with the public.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.

遗传编码材料中心（C-GEM）开发了新的生物启发方法来精确定制和构建聚合物。聚合物由重复的分子单元结合而成，从塑料制品到DNA，无处不在。通过控制分子单元的身份和连接，聚合物的性质可以被微调，这导致了新产品和应用的爆炸式增长。尽管取得了这些进展，但系统地、精确地控制聚合物中分子单元的序列仍然是极其困难的。有了这种控制水平，新的聚合物可以用于信息存储、纺织品和织物、纳米传感器以及药物发现和输送。为了实现这一艰难但具有变革性的化学过程，C-GEM采用了两种互补的方法。首先，C-GEM重新设计核糖体，在分子之间按顺序建立键，就像天然核糖体通过按顺序组装α -氨基酸来构建蛋白质一样。其次，C-GEM有目的地扩展天然多肽的结构，从而显著增加其化学多样性和功能。C-GEM还在化学、生物学和材料科学的丰富新界面上，以合作团队的形式吸引和培训不同群体的学生和博士后研究人员。C-GEM还通过科学发现游戏《EteRNA》吸引公民科学家，向感兴趣的玩家介绍RNA结构、稳定性和功能的关键概念。新的EteRNA挑战集中在核糖体的化学上。总体而言，C-GEM正在建立定制聚合物的未来，以应对健康，环境和工业挑战，促进创新，并在多个化学-生物-材料前沿培养多样化的劳动力。C-GEM的二期研究计划包括相互关联的目标，将扩展核糖体介导的化学，以产生结构和功能独特的分子结构。C-GEM还在寻求一条平行的途径，即创新的“后期功能化”反应将核糖体衍生的产物转化为现有生物合成无法达到的物质。设计、进化和表征翻译分子的新颖和多功能工具将扩大其在体外和体内的化学能力。C-GEM还将使用新的和现有的技术来确定基因编码产物分子和聚合物的结构，以及它们的组装机制。一套计算方法将评估、建模和预测野生型和工程核糖体的化学能力、它们的翻译因子和它们产生的聚合物的性质，标志着计算生物材料设计的新时代的到来。我们的目标还包括制备有用数量的序列定义化学聚合物的策略，从而实现影响生物技术，体内成像，分子医学，材料科学和药物输送的功能。一套多样化的教育和参与计划将研究与培训相结合，建立了多样化的化学劳动力，并与公众接触。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

mRNA decoding in human is kinetically and structurally distinct from bacteria.

• DOI: 10.1038/s41586-023-05908-w
• 发表时间: 2023-05
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Holm, Mikael;Natchiar, S. Kundhavai;Rundlet, Emily J.;Myasnikov, Alexander G.;Watson, Zoe L.;Altman, Roger B.;Wang, Hao-Yuan;Taunton, Jack;Blanchard, Scott C.
• 通讯作者: Blanchard, Scott C.

Minimization of the E. coli ribosome, aided and optimized by community science

• DOI: 10.1093/nar/gkad1254
• 发表时间: 2024-01-12
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Tangpradabkul，Tiyaporn;Palo，Michael;Schepartz，Alanna
• 通讯作者: Schepartz，Alanna