The Sc2.0 UK Genome Engineering Resource (SUGER)

Sc2.0 英国基因组工程资源 (SUGER)

• 批准号: BB/K019791/1
• 负责人: Thomas Ellis
• 金额: $ 124.96万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK019791%2F1
• 关键词: Sc2.0; UK; Genome; Engineering; Resource

Sc2.0 (Synthetic Yeast) is an international flagship project to complete the first chemical synthesis and assembly of a eukaryotic genome, that of the yeast Saccharomyces cerevisiae. The project is an open-access, academic response to genome synthesis work by Craig Venter and others and will make highly-evolvable synthetic yeast strains and new genome-scale engineering methods available to all. The Sc2.0 UK Genome Engineering Resource (SUGER) is a proposed resource that not only enables UK participation in the Sc2.0 project but will also maximise the impact Sc2.0 has on biosciences research, synthetic biology and industrial biotechnology in the UK and abroad. The Sc2.0 international consortium now includes the UK who will lead on the synthesis and assembly of Chromosome XI. The project arises from work led by Jef Boeke at Johns Hopkins University published in Nature last year (Dymond et al). This publication showed completion of two chromosome arms and highlighted many unique modifications designed into the synthetic genome. Three of these of note are (i) eliminating all TAG codons to allow future "orthogonal" encoding of unnatural amino acids, (ii) removing non-essential and destabilising elements (introns, cryptic ORFs, transposons) to streamline the genome and (iii) placing synthetic recombination sites downstream of all non-essential genes. The latter of these is an especially useful tool, as recombination leads to these genes being removed, inverted or translocated within the genome. This novel tool can be used to rapidly evolve cells down to their minimal gene number or to produce arrangements that have increased fitness in desired environments (e.g. biofuel production). Taken together, the Sc2.0 project offers a unique way to explore genome topology, nuclear structure and will also allow researchers to uncover 'context rules' for genome design. It is also a grand challenge project to push boundaries in synthetic biology and modern biosciences. The Sc2.0 website is: http://www.syntheticyeast.orgThe Sc2.0 UK Genome Engineering Resource (SUGER) gives UK participation in this project and will make all DNA, strains, data and genome engineering methods and tools developed during Sc2.0 available to the wider bioscience community as a significant resource. Dr Tom Ellis and Prof Paul Freemont will direct a chromosome team at the synthetic biology centre at Imperial College London to complete design, synthesis, assembly and verification of Chromosome XI by 2016; adding this to the full international set to produce the complete Sc2.0 strain by 2017. Dr Alistair Elfick (Edinburgh) will assist in the process, which will also includes a suite of related bioinformatics software tools and detailed genome engineering protocols. Prof Steve Oliver (Cambridge) will provide world-leading expertise on yeast and direct experiments that will provide quality control and fitness data for hybrid and synthetic yeast chromosomes.SUGER will:1. Complete full synthesis, assembly and verification of Synthetic Yeast Chromosome XI (SynXI - 0.67Mbp) as the UK's contribution to the international Sc2.0 project.2. Curate and distribute a Sc2.0 strain resource, a physical collection for IP-free distribution of S. cerevisiae strains containing the hybrid and fully-synthetic chromosomes of the international Sc2.0 project and the DNA building blocks that were used in construction.3. Extend Sc2.0 resources to be valuable legacy for the wider biosciences community. We will build a SUGER website hosting Sc2.0 and genome engineering information, extend the suite of Sc2.0 software tools and protocols to be applicable for future synthetic biology projects, and run three annual genome engineering workshops for teaching genome-scale synthetic biology concepts and methods to UK researchers.We expect high use of these resources from epigenetics, genomics and yeast researchers as well as from systems biology, synthetic biology and industrial biotech.

Sc2.0（合成酵母）是一个国际旗舰项目，旨在完成真核基因组（酿酒酵母）的首次化学合成和组装。该项目是对 Craig Venter 等人的基因组合成工作的开放获取的学术回应，将为所有人提供高度进化的合成酵母菌株和新的基因组规模工程方法。 Sc2.0 英国基因组工程资源 (SUGER) 是一项拟议资源，不仅使英国能够参与 Sc2.0 项目，而且还将最大限度地发挥 Sc2.0 对英国和英国的生物科学研究、合成生物学和工业生物技术的影响。国外。 Sc2.0 国际联盟现在包括英国，该联盟将领导 XI 染色体的合成和组装。该项目源于约翰·霍普金斯大学 Jef Boeke 领导的去年在《自然》杂志上发表的研究成果（Dymond 等人）。该出版物展示了两条染色体臂的完成，并强调了设计到合成基因组中的许多独特修饰。其中三个值得注意的是 (i) 消除所有 TAG 密码子，以允许未来对非天然氨基酸进行“正交”编码，(ii) 删除非必需和不稳定的元件（内含子、神秘 ORF、转座子）以简化基因组，以及 (iii) ）将合成重组位点置于所有非必需基因的下游。后者是一种特别有用的工具，因为重组会导致这些基因在基因组内被移除、倒置或易位。这种新颖的工具可用于快速进化细胞使其基因数量降至最低，或产生在所需环境（例如生物燃料生产）中具有更高适应性的排列。总而言之，Sc2.0 项目提供了一种探索基因组拓扑、核结构的独特方法，也将使研究人员能够揭示基因组设计的“背景规则”。这也是一个突破合成生物学和现代生物科学界限的重大挑战项目。 Sc2.0 网站是：http://www.syntheticyeast.orgSc2.0 英国基因组工程资源 (SUGER) 让英国参与该项目，并将在 Sc2 期间开发所有 DNA、菌株、数据和基因组工程方法和工具.0 作为重要资源可供更广泛的生物科学界使用。 Tom Ellis 博士和 Paul Freemont 教授将指导伦敦帝国理工学院合成生物学中心的染色体团队，到 2016 年完成 XI 染色体的设计、合成、组装和验证；将其添加到完整的国际系列中，以便在 2017 年生产出完整的 Sc2.0 菌株。Alistair Elfick 博士（爱丁堡）将协助这一过程，其中还包括一套相关的生物信息学软件工具和详细的基因组工程方案。 Steve Oliver 教授（剑桥）将提供世界领先的酵母专业知识和直接实验，为杂交和合成酵母染色体提供质量控制和适应性数据。SUGER 将：1。完成合成酵母染色体XI (SynXI - 0.67Mbp)的全合成、组装和验证，作为英国对国际Sc2.0项目的贡献。2．策划和分发 Sc2.0 菌株资源，这是一个用于免 IP 分发酿酒酵母菌株的物理集合，其中包含国际 Sc2.0 项目的杂交和全合成染色体以及构建中使用的 DNA 构建块。 3 。将 Sc2.0 资源扩展为更广泛的生物科学界的宝贵遗产。我们将建立一个托管 Sc2.0 和基因组工程信息的 SUGER 网站，扩展 Sc2.0 软件工具和协议套件以适用于未来的合成生物学项目，并举办三届年度基因组工程研讨会，教授基因组规模的合成生物学概念和方法给英国研究人员。我们期望表观遗传学、基因组学和酵母研究人员以及系统生物学、合成生物学和工业生物技术充分利用这些资源。

项目成果

The Synthetic Genome Summer Course.

合成基因组暑期课程。

• DOI: http://dx.10.1093/synbio/ysy020
• 发表时间: 2018
• 期刊: Synthetic biology (Oxford, England)
• 作者: Blount BA

Synthetic yeast chromosome XI design provides a testbed for the study of extrachromosomal circular DNA dynamics

合成酵母 XI 染色体设计为染色体外环状 DNA 动力学研究提供了试验平台

• DOI: http://dx.10.1016/j.xgen.2023.100418
• 发表时间: 2023
• 期刊: Cell Genomics
• 作者: Blount B

GC Preps: Fast and Easy Extraction of Stable Yeast Genomic DNA.

GC 制备：快速、轻松地提取稳定的酵母基因组 DNA。

• DOI: http://dx.10.1038/srep26863
• 发表时间: 2016
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Blount BA

Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker's Yeast

面包酵母中抗生素非核糖体肽青霉素的生物合成

• DOI: http://dx.10.1101/075325
• 发表时间: 2016
• 作者: Awan A

Bricks and blueprints: methods and standards for DNA assembly.

砖块和蓝图：DNA 组装的方法和标准。

• DOI: http://dx.10.1038/nrm4014
• 发表时间: 2015
• 期刊: Nature reviews. Molecular cell biology
• 作者: Casini A