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

2010年，研究人员构建了一种合成细菌细胞，其基因组是从实验室化学品中合成的。人们预计，第一个合成细胞将被世界各地的科学家建造的许多其他细胞所取代。事实上，研究人员预计，所有类型的细菌将被设计和构建，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。这还没有发生，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，基因组移植程序的最初发明者将调整该技术，以便它可以应用于其他细菌。这将使学术和工业细菌学家和合成生物学家能够构建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，并将用作与科学界、工业界和公众讨论的平台。基因组移植，将完整的细菌基因组插入合适的受体细胞中，以便捐赠的基因组命令受体细胞产生具有捐赠基因组的基因型和表型的新细胞，是能够构建第一个具有合成基因组的细菌的基本技术发展。在宣布世界上第一个合成细胞JCVI-syn 1.0诞生时，这项工作被誉为人类的一项重大成就。迄今为止，基因组移植仅使用称为支原体的一小部分非典型细菌实现。 该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，并使用微流体技术来自动化和提高基因组移植的效率。 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它来移植分离的完整合成细菌基因组，并产生具有所需特性的新合成细胞。该奖项反映了NSF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。

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.