Developing Genome Transplantation for Non-mycoplasma Bacteria to Enhance the Creation of Synthetic Cells

开发非支原体细菌基因组移植以增强合成细胞的产生

• 批准号: 2218507
• 负责人: John Glass
• 金额: $ 102.53万
• 依托单位: J. Craig Venter Institute, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2218507&HistoricalAwards=false
• 关键词: Developing; Genome; Transplantation; Non; mycoplasma

In 2010, researchers constructed a synthetic bacterial cell whose genome was synthesized from laboratory chemicals. It was anticipated that this first synthetic cell would be followed by many others constructed by scientists all over the world. Indeed, researchers anticipated that bacteria of all types would be designed and constructed to solve human problems in medicine, energy, industry, environmental remediation and basic research. That has yet to happen because it is difficult to transplant a rationally designed synthetic genome into a suitable recipient bacterial cell. In the project proposed here, the original inventors of the genome transplantation procedure will adapt the technique so that it can be applied to other bacteria. This will allow academic and industrial bacteriologists and synthetic biologists to build new bacteria with remarkable capabilities. In addition to removing a huge technical hurdle stalling the construction of synthetic cells, this project will facilitate the training of the next generation of scientists in the field of synthetic biology and will be used as a platform for discussions with the scientific community, industry and public. Genome Transplantation, the insertion of a complete bacterial genome into a suitable recipient cell so that the donated genome commandeers the recipient cell to produce a new cell with the genotype and phenotype of the donated genome, was the fundamental technical development that enabled the construction of the first bacterium with a synthetic genome. At the announcement of the creation of the world’s first synthetic cell, JCVI-syn1.0, the work was heralded as a major accomplishment for humans. To date, genome transplantation has only been achieved using a small subset of the atypical bacteria called mycoplasmas. The goals of this project are to investigate the mechanism of genome transplantation, develop genome transplantation for at least two species of non-mycoplasma bacteria, and use microfluidics technology to automate and improve the efficiency of genome transplantation. A potential outcome is to establish a set of rules that synthetic cell builders can use to transplant isolated whole synthetic bacterial genomes and produce new synthetic cells with desired properties.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.

2010年，研究人员构建了一个人工合成的细菌细胞，其基因组是用实验室化学物质合成的。人们预计，在这第一个合成细胞之后，世界各地的科学家将制造出许多其他的细胞。事实上，研究人员预计，所有类型的细菌都将被设计和构建，以解决人类在医学、能源、工业、环境修复和基础研究方面的问题。这还没有实现，因为很难将合理设计的合成基因组移植到合适的受体细菌细胞中。在这里提出的项目中，基因组移植程序的原始发明者将调整该技术，使其可以应用于其他细菌。这将使学术界和工业界的细菌学家和合成生物学家能够培育出具有非凡能力的新细菌。除了消除阻碍合成细胞构建的巨大技术障碍外，该项目还将促进合成生物学领域下一代科学家的培训，并将被用作与科学界、工业界和公众讨论的平台。基因组移植是将完整的细菌基因组插入到合适的受体细胞中，使捐赠的基因组支配受体细胞产生具有捐赠基因组基因型和表型的新细胞，这是使第一个具有合成基因组的细菌得以构建的基本技术发展。在宣布世界上第一个合成细胞JCVI-syn1.0诞生时，这项工作被誉为人类的一项重大成就。迄今为止，基因组移植只使用了一小部分被称为支原体的非典型细菌。本项目的目标是研究基因组移植的机制，开发至少两种非支原体细菌的基因组移植，并利用微流体技术实现基因组移植的自动化和效率的提高。一个潜在的结果是建立一套规则，合成细胞构建者可以使用这些规则来移植分离的整个合成细菌基因组，并产生具有所需特性的新合成细胞。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。