Collaborative Research: Synthetic and Systems Biology Approaches to Semi-synthetic Cells with Expanded DNA Alphabets

合作研究：具有扩展 DNA 字母表的半合成细胞的合成和系统生物学方法

• 批准号: 2123995
• 负责人: Steven Benner
• 金额: $ 120万
• 依托单位: Foundation for Applied Molecular Evolution, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2123995&HistoricalAwards=false
• 关键词: Collaborative; Research; Synthetic; Systems; Biology

This project focuses on novel forms of DNA that are not built only from the standard four nucleotides found in natural DNA, but with two or four additional nucleotides, to form an "Artificially Expanded Genetic Information System" (AEGIS). Expanded DNA has already seen widespread use in human diagnostics and environmental surveillance for pathogens. This project will break new ground in developing our understanding of DNA, and develop new technology for business, defense, and health. It will do so by studying the interaction of AEGIS DNA and its components with living microbial cells. As AEGIS can support Darwinian evolution, seen by many as the essence of life, this project will drive a deeper understanding of life. Further, it will allow laboratory evolution of new functional materials, adding evolution and adaptation to points in biotechnology where description and design are inadequate. Finally, this project emphasizes public outreach efforts and the training of early career scientists. This project will complete engineering of bacterial strains that replicate, evolve, and use DNA built not from 4 different nucleotides, but from 6 or 8, DNA in an Artificially Expanded Genetic Information System (AEGIS). These strains, "Second Examples of Genetics Undergoing Evolution" (SEGUE) will use one (or both) of two 6-letter genetic alphabets, GACTKX and GACTZP. A multidisciplinary team of chemists, molecular biologists, philosophers, and bioengineers will exploit comprehensive preliminary data. Here, critical points are integrated to yield results beneficial across multiple platforms:• Broader Impacts in training, outreach, and risk analysis by having direct contact between experiments and those who study the history of and "science of" science.• Work to develop polymerases that replicate AEGIS DNA in vitro and in vivo SEGUE. These will themselves have value in environmental pathogen surveillance, diagnostics, and therapeutic development, as well as the creation of new materials for biotechnology.• Protein engineering to build a metabolic pathway to biosynthesize, inside of living cells, AEGIS triphosphates, allowing AEGIS to be used inexpensively.• Study of interactions between AEGIS and living cells, specifically to identify "third party" genes and regulatory systems that improve the performance and lower the cost of AEGIS in SEGUE.• Broader impacts include the training of experimental scientists in philosophical and ethical features of synthetic biology, iGEM projects, and training for undergraduate and graduate students. The implications throughout science are enormous, and touch on concepts of shadow biospheres, life on Mars and elsewhere in the Solar System, and how life in general is conceived and understood by scientists and the general public alike. Two updated books will provide a framework for thinking about these and other issues, Cleland's "The Quest for a Universal Theory of Life" and Benner's "Life, the Universe, and the Scientific Method." Other outreach materials will include the blog: "Primordial Scoop", which discusses science and technology from philosophical and ethical perspectives. Educational materials will be internationally available, including in classrooms, museums, and planetariums.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.

该项目的重点不仅是在天然DNA中发现的标准fourd，但具有两个或四个L核苷酸，以形成“人为扩展的遗传遗传信息系统”（AEGIS）。对于DNA的病原体，并开发了用于业务，防御和健康的新技术。进一步，它将允许实验室进化，并在生物技术和设计中适应了cientists的点。人为扩展的遗传信息系统（宙斯盾）。多个平台：•通过直接接触Ween实验以及研究“科学和科学的历史。EM自己对环境病原体监测，诊断和治疗性发展以及治疗性的发展以及研究的历史，也有价值，对培训，外展和风险分析的更广泛影响，以及生物技术的新材料•蛋白质工程建立了生物合成的代谢途径，在活细胞内部，较低的AEGIS以廉价地使用•研究了“第三方”和“第三方”基因和活细胞的相互作用。监管系统的性能并降低合成的n哲学和道德特征，并为本科生的培训变得越来越多。 STS和公众都将提供一个框架，以思考其他Issues，Cleland的“对生命的追求”，“宇宙”和“科学方法”。从哲学和道德的角度讨论科学和技术。审查标准。