SYNTHETIC GENOME: REWRITING THE CODE OF LIFE
FALAK C. PANDIT -INSTITUTE OF SCIENCE, NIRMA UNIVERSITY, AHMEDABAD Email-falakchirag@gmail.com, 9106737519
ABSTRACT
In Genomics, revealing the mystery of the code of life that is DNA (Deoxy-ribonucleic acid) has always been the subject of study. From Sanger sequencing to the Automated next generation sequencing methods, this field has now advanced to the synthesis of artificial DNA and its assembly to produce the Synthetic cells. Earlier experimentations emphasized on synthesis of small viral genomes followed by wild-type bacterial genomes thereafter transplantation of this genome into closely related strains. The recent implications include designing of the Synthetic promoters, Evolution of Yeast genome and therapeutic effects. This poster discusses the overall History, Development and Applications of synthetic genome from the Research Papers.
First Synthetic Eukaryotic Organism
Creation of First Cell with Synthetic Genome In 1977, Sanger and colleagues determined the entire genetic sequence of phage ϕX174,which was the first DNA genome to be completely sequenced. In 2010, Craig Venter and team successfully created JCVI-syn 1.0 genome and transplanted into M. capricolum (recipient) to create new M. mycoides cells which were solely controlled by synthetic genome. The only DNA in the cells was the designed DNA along with the watermark sequences and other deletions and polymorphism in the genes. The new cells had expected phenotypic properties and were capable of continuous self-replication. (Gibson et. al 2010)
The idea for designing and synthesizing a eukaryotic chromosome was carried out in 2007. The 30kbp fragment chromosome III was first designed and synthesized further replacing the wild-type segment with the synthetic piece in yeast. The yeast used was S. cerevisiae. Later on the more development was done synIII was synthesized and project Sc2.0 was carried out. The synIII chromosome is about 2.5 % of the yeast genome and the changes that were made were all conservative, although numerous. The design and synthesis of synIII is shown in figure. (Annaluru et. al 2015)
Prosthetic” cell implants to control glucose levels by blue light in a mouse model of human type-2 diabetes (Ye H et. al 2011)
Synthetic mutagenic triplex-forming molecules and their genomic targeting sites. (Reza et. al 2015)
Timeline for milestones of Synthetic Genome
Applications 1. 2. 3. 4. 5. 6. 7.
Synthetic gene circuits for drug discovery and prosthetic devices. Therapeutic Synthetic RNA devices. GE Viruses and bacteria. GE Mosquitoes for Disease control Synthetic antigens. Synthesized/altered viral genomes or vaccines. Designed pathways to diseases such as cancer and malaria. (egTaxol and artemisinin) The reality for Minimal Genome Concept and can be designed Successfully by removing unnecessary sequences. Newer Biosynthetic pathways to produce biofuels, alcohol and detox agents. Metabolic Pathways can be redesigned according to functional requirement or to cure disease.
1.Gibson, Daniel G., et al. "Creation of a bacterial cell controlled by a chemically synthesized genome." science 329.5987 (2010): 52-56. 2.Annaluru, Narayana et al. “Rewriting the blueprint of life by synthetic genomics and genome engineering.” Genome biology vol. 16,1 125. 16 Jun. 2015, doi:10.1186/s13059-015-0689-y 3. König, Harald et al. “Synthetic genomics and synthetic biology applications between hopes and concerns.” Current genomics vol. 14,1 (2013): 11-24. doi:10.2174/1389202911314010003 4. Ye H, Daoud-El Baba M, Peng R W, Fussenegger M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science. 2011;332:1565–1568 5. Reza, Faisal, and Peter M Glazer. “Therapeutic genome mutagenesis using synthetic donor DNA and triplex-forming molecules.” Methods in molecular biology (Clifton, N.J.) vol. 1239 (2015): 39-73. doi:10.1007/978-1-4939-18621_4