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Darwinism from Artificial Genomes

来自人工基因组的达尔文主义

基本信息

批准号：
1939086
负责人：
Steven Benner
金额：
$ 137.41万
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：
2019
资助国家：
美国
起止时间：
2019-12-15 至 2024-11-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1939086&HistoricalAwards=false
关键词：
Darwinism Artificial Genomes

项目摘要

A decade ago, NASA commissioned the National Academy to survey what was known about the limits of life, develop a general theory of life, and suggest ways that alien life might be found in the cosmos. The Academy recommended that synthetic biology be a tool to address such big questions in life science. Synthetic biology goes beyond descriptive biology, which investigates only the one example of life that the natural history on earth has given us. This project implements synthetic biology to examine the plausibility of alternatives to DNA, which is the primary unit of heredity of life on earth. This project also emphasizes a public outreach effort and the training of early career scientists. A novel synthetic chemical system that supports Darwinian evolution will be delivered through this project, which fits the MCB emphasis on "synthetic biology…capturing the power of mechanistic, quantitative, and evolutionary approaches". The "alien" Darwinian biopolymer will have four informational building blocks (PZBS, hypothesized as an optimal number), a polyelectrolyte backbone (hypothesized necessary for Darwinism), and inter-heterocycle hydrogen bonding (hypothesized required for directionality) in the transfer of genetic information as standard GACT DNA does. This will be the first example of a Darwinian system that does not include any natural building blocks. Further, PZBS DNA adds "skinny" and "fat" pairing to Watson-Crick size-complementary pairing, informational structures and functionality unavailable to standard GACT DNA. PZBS DNA will be synthesized chemically and characterized. Polymerases to support PZBS biopolymers amplification will be evolved by compartmentalized self-replication. For sequencing, a transliteration technique to sequence GACTPZ six-letter DNA will be used; creative re-purposing of this will sequence PZBS DNA. PZBS libraries will then be placed under selection pressure to evolve functional PZBS molecules. Crystallography will be applied throughout to advance nucleic acid theory as the PZBS system is advanced.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.

十年前，美国宇航局委托美国国家科学院调查已知的生命极限，发展生命的一般理论，并提出在宇宙中发现外星生命的方法。该学院建议将合成生物学作为解决生命科学中此类重大问题的工具。合成生物学超越了描述生物学，描述生物学只研究地球自然历史给我们的唯一一个生命例子。该项目利用合成生物学来检验 DNA 替代品的合理性，DNA 是地球上生命遗传的主要单位。该项目还强调公共宣传工作和对早期职业科学家的培训。该项目将提供支持达尔文进化论的新型合成化学系统，这符合 MCB 强调的“合成生物学……捕捉机械、定量和进化方法的力量”。 “外星”达尔文生物聚合物将像标准 GACT DNA 一样，在遗传信息传递中具有四个信息构建块（PZBS，假设为最佳数量）、聚电解质主链（假设为达尔文主义所必需）和杂环间氢键（假设为方向性所需）。这将是不包含任何自然构件的达尔文系统的第一个例子。此外，PZBS DNA 在 Watson-Crick 尺寸互补配对、标准 GACT DNA 无法提供的信息结构和功能中添加了“瘦”和“胖”配对。 PZBS DNA 将进行化学合成并进行表征。支持 PZBS 生物聚合物扩增的聚合酶将通过区室化自我复制而进化。对于测序，将使用音译技术对 GACTPZ 六字母 DNA 进行测序；对此进行创造性的重新利用将对 PZBS DNA 进行测序。然后，PZBS 文库将面临选择压力，以进化出功能性 PZBS 分子。随着 PZBS 系统的进步，晶体学将始终应用于推进核酸理论。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。