We will set up an international collaboration to continue our pioneer work to synthesize the first re-coded eukaryotic genome (the Sc2.0 project):

    The famous quote from the physicist Richard Feynman ??What I cannot create, I do not understand?? demonstrates well that the ultimate understanding of the nature will lead to the ability of creating new matters, and in turn the creation will contribute to a better understanding. Biology is now undergoing a transition from the age of deciphering DNA sequence information of the genome of biological species to an age of building synthetic genomes to better understand the principles of life. This transition has been formalized as a new discipline referred to as ??Synthetic Biology?? (SynBio). Despite its early stage, SynBio has already shown great potential to make significant scientific breakthrough, which will improve the living conditions of human beings. For example, engineering metabolic pathways of yeast to produce the antimalarial drug precursor artemisinic acid; using engineered microorganisms to convert biomass to biofuel as a replacement of fossil fuel; and utilizing engineered bacteriophage as adjuvants for antibiotic therapy. In early 2010, the Venter Institute reported that they have designed and chemically synthesized a near-native mycoplasma mycoides genome (JVCI-syn1.0, 1.08M base pair), and successfully used this synthetic genome to replace the natural genome of a M.capricolum cell to take over the control of this bacterial cell using a technique called ??genome transplantation.?? The ability to design and synthesize synthetic genomes opens up the possibility to develop microbial solutions to societal problems such as energy crisis. In collaboration with several labs around the world, we are contributing to the largest synthetic biology project ever - the Sc2.0 project (Dymond JS, Nature, 2011):

  1. We will develop methodology to reduce the cost of oligo synthesis. The major bottleneck to limit large-scale gene synthesis at current stage is the cost to make oligoes. In addition, the error rate in oligo synthesis prevents us from making high-fidelity long DNA sequences from oligoes. Recently the Church lab at Harvard published a serial of papers to overcome these limitations. Based on these results, we will develop a protocol to apply these methods in our whole chromosome synthesis and eventually an automatic, high-throughput method to expedite the synthesis process and reduce the cost.
  2. We will design, synthesize and assemble yeast Chromosome XII. Due to our special interest in ribosomal RNA gene region, we will focus on the synthesis of Chromosome XII, which is the largest chromosome in yeast (~2 million base pairs). About 50% of the chromosome is composed of ribosomal RNA genes, which includes 100-150 copies of repetitive sequences. We will work on the rDNA repeat at first by replacing the genomic copies of rDNA gene with the synthetic ones. Then we will redesign the chromosome aimed at a) maintaining a wild-type phenotype, b) producing a more stable genome by removing the destabilizing elements such as transposons, c) embedding elements designed to maximize future genetic flexibility such as recoding the stop code TAG to TAA and the incorporation of symmetrical loxP sites throughout the chromosome.