Team:ETH Zurich

"This year's ETH Zurich project tackles a fundamental problem of synthetic biology: the minimal genome. Exploring the minimal set of genes that is able to support life is not only a question of significant biological interest, it is also a crucial step towards the implementation of orthogonal functionalities into a rationally designed complex biological system. An organism carrying a minimal genome would provide a simple chassis for biological engineering. We attempted to exploit the power of accelerated evolution for a genome reduction strategy. Our approach is based on an iterative cycle of genome reduction and strain selection. We propose a novel method to randomly delete chromosomal DNA fragments by controlled expression of restriction enzymes and ligases in vivo. Furthermore, we develop a chemostat-based condition to select for cells with a smaller genome size by constraining nucleotide availability. Computationally, we analyze the genome for the optimal restriction enzyme, and perform flux balance analysis on a genome scale model to predict growth of reduced genome strains. Finally, we simulate the restriction enzyme expression and the progression of selection."