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The Sc2.0 UK Genome Engineering Resource (SUGER)

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:
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
项目状态:
已结题
起止时间:
2013 至 --

项目摘要

项目成果

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中文摘要
翻译
Sc2.0 (Synthetic Yeast)是一项国际旗舰项目,旨在完成真核生物酵母(Saccharomyces cerevisiae)基因组的首次化学合成和组装。该项目是对Craig Venter等人基因组合成工作的一个开放获取的学术回应,将使高度可进化的合成酵母菌株和新的基因组规模工程方法可供所有人使用。Sc2.0英国基因组工程资源(SUGER)是一项提议的资源,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对英国国内外生物科学研究、合成生物学和工业生物技术的影响。Sc2.0国际联盟现在包括英国,它将领导第11号染色体的合成和组装。该项目源于约翰霍普金斯大学的jeff Boeke去年在《自然》杂志上发表的研究成果(Dymond等)。该出版物展示了两条染色体臂的完成,并突出了许多独特的修饰设计到合成基因组中。其中三个值得注意的是:(i)消除所有TAG密码子,以便将来对非天然氨基酸进行“正交”编码;(ii)去除非必需和不稳定元素(内含子、隐性orf、转座子),以简化基因组;(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中被移除、反转或易位。这种新颖的工具可以用来快速地将细胞进化到最小的基因数量,或者产生在所需环境中增加适应性的排列(例如生物燃料生产)。总的来说,Sc2.0项目提供了一种独特的方式来探索基因组拓扑结构、核结构,也将允许研究人员发现基因组设计的“上下文规则”。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的网站是:http://www.syntheticyeast.orgThe Sc2.0英国基因组工程资源(SUGER)让英国参与到这个项目中,并将把在Sc2.0期间开发的所有DNA、菌株、数据和基因组工程方法和工具作为重要资源提供给更广泛的生物科学界。汤姆·埃利斯博士和保罗·弗里蒙特教授将在伦敦帝国理工学院合成生物学中心领导一个染色体团队,在2016年之前完成第11号染色体的设计、合成、组装和验证;将其添加到到2017年生产完整的Sc2.0菌株的完整国际集合中。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协议。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,为杂交酵母和合成酵母染色体提供质量控制和适应性数据。苏格将:1。作为英国对国际Sc2.0项目的贡献,完成了合成酵母染色体XI (SynXI - 0.67Mbp)的全合成、组装和验证。管理和分发Sc2.0菌株资源,这是一个物理收集,用于无ip分布的酿酒酵母菌株,其中包含国际Sc2.0项目的杂交和全合成染色体以及用于构建的DNA构建块。扩展Sc2.0资源,使其成为更广泛的生物科学界的宝贵遗产。我们将建立一个容纳Sc2.0和基因组工程信息的网站,扩展Sc2.0软件工具和协议套件,使其适用于未来的合成生物学项目,并每年举办三次基因组工程研讨会,向英国研究人员教授基因组规模的合成生物学概念和方法。我们期待表观遗传学、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人员对这些资源的高度利用。
英文摘要
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.
期刊论文(10)
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科研奖励(0)
会议论文
The Synthetic Genome Summer Course.
合成基因组暑期课程。
DOI: 10.1093/synbio/ysy020
发表时间: 2018
期刊: Synthetic biology (Oxford, England)
影响因子: --
作者: [Blount BA]
通讯作者: Blount BA
DOI: 10.1038/srep26863
发表时间: 2016-05-31
期刊: Scientific reports
影响因子: 4.6
作者: [Blount BA, Driessen MR, Ellis T]
通讯作者: Ellis T
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