AUG 20, 2014 08:45 AM PDT

Digitizing Life Using Synthetic Genomics

  • Senior Scientist, Synthetic Biology Group, J. Craig Venter Institution
      John Glass is a Professor in and leader of the JCVI Synthetic Biology and Bioenergy Group.  His expertise is in molecular biology, microbial pathogenesis, RNA virology, and microbial genomics. Glass is part of the Venter Institute team that created a synthetic bacterial cell in 2010. In reaching this milestone the Venter Institute scientists developed the fundamental techniques of the new field of synthetic genomics including genome transplantation and genome assembly.  Glass was also leader of the JCVI project that rapidly made synthetic influenza virus vaccine strains in collaboration with Novartis Vaccines and Diagnostics, Inc. and Synthetic Genomics, Inc. At the JCVI he has also led the bacterial outer membrane vesicle based vaccine, genome transplantation, and Mycoplasma genitalium minimal genome projects, and projects studying other mycoplasma and ureaplasma species. Glass and his Venter Institute colleagues are now using synthetic biology and synthetic genomics approaches developed at the JCVI to create cells and organelles with redesigned genomes to make microbes that can produce biofuels, pharmaceuticals, and industrially valuable molecules. Prior to joining the JCVI in 2003, Glass spent five years in the Infectious Diseases Research Division of the pharmaceutical company Eli Lilly. There he directed a hepatitis C virology group and a microbial genomics group.Glass earned his undergraduate and graduate degrees from the University of North Carolina at Chapel Hill. His Ph.D. work was on RNA virus genetics in the laboratory of Gail Wertz. He was on the faculty and did postdoctoral fellowships in the Microbiology Department of the University of Alabama at Birmingham in polio virology with Casey Morrow and mycoplasma pathogenesis with Gail Cassell (1990-1998). On sabbatical leave in Ellson Chen's lab at Applied Biosystems Inc.(1995-1997) he sequenced the genome of Ureaplasma parvum and began his study of mycoplasma genomics.


    In 2010, our team of synthetic biologists announced the creation of a bacterial cell that had a chemically synthesized genome. To build this synthetic Mycoplasma mycoides JCVI 1.0 we had to develop two sets of methods. The path to develop what we believe will be the foundation technologies of the field of Synthetic Genomics took ~150 man year and many twists and turns. We made the 1.1 Mbp M. mycoides genome using a series of new techniques for assembly of DNA molecules in vivo in yeast cells and in vitro. This process we called Genome Assembly. The other new technical repertoire is Genome Transplantation. We isolated our synthetic genome, which was cloned as a yeast artificial chromosome, and installed it into cells of a closely related bacterial species. We are currently eliminating all the genes in this organism not essential for growth in the laboratory. We expect to produce a cell with less than 400 protein-coding genes. This minimal bacterium will likely have about 100 genes of unknown function, and most of those will have homologous genes in most other bacteria. We plan to use this simple organism to investigate the fundamental principles of cellular life. The Synthetic Genomics technology developed from this effort will enable biologists to build both microbes as well as eukaryotic cells capable of solving human needs in medicine, bioenergy and industry. For instance we envision the same Genome Assembly and Genome Transplantation technologies used to build synthetic microbial cells could be used to make human artificial chromosomes and install them in cells for therapeutic and research purposes.

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