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: 2123996
• 负责人: Andrew Ellington
• 金额: $ 129.97万
• 依托单位: University of Texas at Austin
• 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=2123996&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.

该项目着重于新的DNA形式，这些形式不仅是由天然DNA中发现的标准四个核苷酸建造的，而是使用两个或四个附加核苷酸来形成“人为扩展的遗传信息系统”（AEGIS）。扩展的DNA已经在人类诊断和环境监测中对病原体进行了广泛使用。该项目将在发展我们对DNA的理解并为业务，国防和健康开发新技术方面打破新的基础。它将通过研究AEGIS DNA及其成分与活微生物细胞的相互作用来做到这一点。作为宙斯盾可以支持达尔文进化论，被许多人视为生命的本质，这个项目将推动对生活的更深入的了解。此外，它将允许实验室的新功能材料的进化，从而将演化和适应性增加为描述和设计不足的生物技术中的点。最后，该项目强调了公众的外展工作和对早期职业科学家的培训。该项目将完成不从4种不同的核苷酸中复制，进化和使用DNA的细菌菌株的工程，而是从6或8个DNA中的人为扩展的遗传信息系统（AEGIS）中的6或8个DNA。这些菌株是“正在进化的遗传学的第二个例子”（SEGUE）将使用两个（或两者兼有）两个6个字母的遗传字母，即GACTKX和GACTZP。化学家，分子生物学家，哲学家和生物工程师的多学科团队将探索全面的初步数据。在这里，临界点是整合以在多个平台之间产生有益的结果：•通过实验与研究科学史和“科学”的历史和“科学”的人之间的直接接触，在培训，外展和风险分析中产生更大的影响。•努力开发聚合酶，以开发在体外和体内复制AEGIS DNA的聚合酶。这些本身将在环境病原体的监测，诊断和治疗性发展以及生物技术的新材料中创建新材料。•蛋白质工程能够建立一种代谢途径，以在活细胞内，在活细胞内，三层磷酸盐的aegis群体中，使aegis既可以实现aegis and opertive and opertive in Dexportion”•三分之一的竞争。这可以提高性能并降低盟友在SEGUE中的成本。•更广泛的影响包括对合成生物学，IGEM项目的哲学和道德特征进行实验科学家的培训，以及对本科生和研究生的培训。整个科学的含义都是巨大的，并触及了阴影生物圈的概念，太阳系中的火星和其他地方的生活，以及科学家和公众的一般生活如何构思和理解。两本更新的书籍将提供一个思考这些问题和其他问题的框架，克莱兰德的“追求普遍的生命理论”以及本纳的“生命，宇宙和科学方法”。其他外展材料将包括博客：“原始勺子”，该博客从哲学和道德的角度讨论科学和技术。教育材料将在国际上获得，包括教室，博物馆和天文馆。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为是通过评估来获得珍贵的支持。