Synthesis And Restructuring of a Yeast Chromosome

酵母染色体的合成和重组

• 批准号: 1443299
• 负责人: Jef Boeke
• 金额: $ 63.5万
• 依托单位: New York University Medical Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1443299&HistoricalAwards=false
• 关键词: Synthesis; Restructuring; Yeast; Chromosome

Chemists first probed the structure of matter using analytic approaches, describing what they perceived. They subsequently gained a far more thorough mastery of and insights into chemical compounds by synthesizing them. Biology is now undergoing a similar transition from the age of deciphering DNA sequence information of biological species to a synthetic genome age; this transition demands a whole new level of biological understanding, which has been formalized as the new discipline of "Synthetic Biology" (SynBio). A great deal of energy and effort has been invested by the principal investigators into a new undergraduate course, "Build A Genome", in which students produce the Building Blocks used as starting materials for chromosome assembly. This course will be expanded dramatically by "franchising" it to other Colleges and Universities, thereby engaging a highly motivated workforce directly in the project and providing unparalleled training/learning opportunities for students nationwide, and eventually, internationally. The eventual "synthetic yeast" that will be designed and refined is likely to play an important practical role. Yeasts, and S. cerevisiae in particular, are preeminent organisms for industrial fermentations, with a wide variety of practical uses including ethanol production from agricultural products and by-products. This project uses the model eukaryote S. cerevisiae as the basis for a cell with a synthetic genome "Sc2.0" that can be used to answer a wide variety of profound questions about fundamental properties of chromosomes, genome organization, gene content, the function of RNA splicing, the extent to which small RNAs play a role in eukaryotic biology, the distinction between prokaryotes and eukaryotes, and the intimate relationship between genome structure and evolution. The availability of a fully synthetic genome will allow direct testing of evolutionary questions that are not otherwise approachable. S. cerevisiae is the organism of choice for these studies because the genomic and related resources available are quite simply better than for any other organism. This offers the opportunity to apply extensive yeast systems biology information to the design of chromosomes for the organism. It is anticipated that Sc2.0 will differ from the native organism, and the multitude of genetic assays available for the organism can be used to understand phenotypic differences that might be observed.

化学家首先用分析方法探索物质的结构，描述他们所感知到的东西。随后，他们通过合成化合物，对化合物有了更彻底的掌握和更深入的了解。生物学现在正经历着一个类似的转变，从破译生物物种DNA序列信息的时代到合成基因组时代；这种转变要求对生物学的理解达到一个全新的水平，这已经被正式定义为“合成生物学”（SynBio）的新学科。主要研究人员在一门新的本科课程“构建基因组”上投入了大量的精力和努力。在这门课程中，学生们制作用于染色体组装的基本材料。这门课程将通过“特许经营”的方式扩展到其他学院和大学，从而直接参与到项目中来，并为全国乃至全球的学生提供无与伦比的培训/学习机会。最终设计和提炼的“合成酵母”可能会发挥重要的实际作用。酵母，特别是酿酒酵母，是工业发酵的卓越生物，具有各种各样的实际用途，包括从农产品和副产品中生产乙醇。本项目以酿酒酵母模型真核生物为基础，构建具有“Sc2.0”合成基因组的细胞，该合成基因组可用于回答关于染色体基本特性、基因组组织、基因含量、RNA剪接功能、小RNA在真核生物生物学中的作用程度、原核生物与真核生物的区别以及基因组结构与进化之间的密切关系等一系列深刻问题。一个完全合成的基因组的可用性将允许直接测试进化问题，否则无法接近。酿酒葡萄球菌是这些研究的首选生物，因为它的基因组和相关资源比其他任何生物都要好。这提供了将广泛的酵母系统生物学信息应用于生物体染色体设计的机会。预计Sc2.0将与原生生物不同，并且可用于该生物的大量遗传分析可用于了解可能观察到的表型差异。