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    Five additional synthetic yeast chromosomes completed

    Dai Junbiao, head of Tsinghua University's research team, checks the yeast in the laboratory of Tsinghua University in Beijing, March 9, 2017

    Synthetic biologists have tested one aspect of this notion by engineering chromosomes from scratch, sticking them into yeast and seeing whether the modified organisms can still function normally. According to seven papers published on March 10th in Science, the global Sci.2.0 team has described the creation, testing and refining of five new redesigned yeast chromosomes.  Together with a sixth previously synthesized chromosome, they represent more than one-third of the genome of the baker’s yeast Saccharomyces cerevisiae.

    The global Sci.2.0 team, an international consortium of more than 200 researchers, that created the chromosomes expects to complete a fully synthetic yeast genome by the end of the year. Like computer programmers, scientists add swaths of synthetic DNA to – or remove stretches from – human, plant, bacterial or yeast chromosomes in hopes of averting disease, manufacturing medicines, or making food more nutritious. Yeast has long served as an important research model because their cells share many features with human cells, but are simpler and easier to study.

    “This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry,” says Jef Boeke, the Sc2.0 project director.  “Beyond any one application, the papers confirm that newly created systems and software can answer basic questions about the nature of genetic machinery by reprogramming chromosomes in living cells.”

    In March 2014, Sc2.0 successfully assembled the first synthetic yeast chromosome (synthetic chromosome 3 or synIII) comprising 272,871 base pairs, the chemical units that make up the DNA code. The new round of papers consists of an overview and five papers describing the first assembly of synthetic yeast chromosomes synII, synV, synVI, synX, and synXII. A seventh paper provides a first look at the 3D structures of synthetic chromosomes in the cell nucleus which mimic their native counterparts with remarkable fidelity.

    The package of seven newly published had authors from ten universities in several countries, including the US (NYU Langone, Johns Hopkins), China (Tsinghua, Tianjin), France (Institut Pasteur, Sorbonne Universités), and Scotland (Edinburgh); along with authors from key industry partners: BGI, the leading Chinese genomics company, and US/China-based Genscript.

    Led by the School of Chemical Engineering and Technology at Tianjin University in China, the paper describing the synthesis of SynV is noteworthy in that is was done by undergraduate students as part of “Build-a-Genome China”, a class first taught in the United States at Johns Hopkins, where Boeke worked before coming to NYU Langone. This is part of an emerging global network of “chromosome foundries,” says Boeke, “which is building the next generation of synthetic biologists along with chromosomes.” The Tianjin group also notably completed two chromosomes, and developed powerful methods for “debugging” errors found in synthetic chromosomes.

    In addition to Boeke and Mitchell, lead organizers for the current studies included Ying-Jin Yuan of Tianjin and Junbiao Dai of Tsinghua University, Joel Bader from Johns Hopkins, Romain Koszul at the Institut Pasteur, Yizhi Cai at the University of Edinburgh, and Huanming Yang at BGI. The US studies were supported principally by the National Science Foundation. Other key funding sources were the China National High Technology Research and Development Program, the National Science Foundation of China, the Chinese Ministry of Science and Technology, the UK Biotechnology and Biological Sciences Research Council, and ERASynBio.

    Links to seven papers:

    1. Design of a synthetic yeast genome

    2. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

    3. “Perfect” designer chromosome V and behavior of a ring derivative

    4. Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond

    5. Bug mapping and fitness testing of chemically synthesized chromosome X

    6. Engineering the ribosomal DNA in a megabase synthetic chromosome

    7. 3D organization of synthetic and scrambled chromosomes

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