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.

化学家首先使用分析方法探索物质的结构，描述他们的感知。随后，他们通过合成化合物，对化合物有了更彻底的掌握和了解。生物学现在正在经历类似的转变，从破译生物物种DNA序列信息的时代到合成基因组时代；这种转变需要对生物学的理解达到一个全新的水平，这已被正式确定为“合成生物学”（SynBio）这一新学科。 主要研究人员投入了大量的精力和精力在一门新的本科课程“构建基因组”上，学生们在课程中制作用作染色体组装起始材料的构建模块。该课程将通过“特许经营”给其他学院和大学来大幅扩展，从而使积极主动的劳动力直接参与该项目，并为全国乃至国际学生提供无与伦比的培训/学习机会。最终将被设计和提炼的“合成酵母”很可能发挥重要的实际作用。酵母，特别是酿酒酵母，是工业发酵的杰出生物体，具有广泛的实际用途，包括从农产品和副产品生产乙醇。该项目使用真核生物酿酒酵母模型作为具有合成基因组“Sc2.0”的细胞的基础，该细胞可用于回答有关染色体基本特性、基因组组织、基因内容、功能的各种深刻问题。 RNA剪接的原理、小RNA在真核生物学中发挥作用的程度、原核生物和真核生物之间的区别，以及基因组结构和进化之间的密切关系。完全合成的基因组的可用性将允许直接测试其他方式无法解决的进化问题。酿酒酵母是这些研究的首选生物体，因为可用的基因组和相关资源比任何其他生物体都要好。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 将与天然生物体不同，并且可用于该生物体的多种遗传测定可用于了解可能观察到的表型差异。