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Over the last 12 years, my lab has been building synthetic yeast chromosomes from scratch. These synthetic genomes are engineered to allow genome-wide directed evolution with a system call SCRaMbLE (Synthetic Chromosome Recombination and Modification by LoxP-Mediated Evolution). SCRaMbLE allows the synthetic cells to process the information (e.g. environmental stress) differently from their wildtype counterparts, and also enables them to re-configure the genomes to cope with the environments. I will present our latest progress in design, synthesis and transplant synthetic chromosomes and its applications. Finally, I will also discuss the progress of developing biocontainment strategies for synthetic genomes.