Streamlining synthetic genomes for designer organisms

The Sc2.0 International Synthetic Yeast Genome Project is finalising the construction of the first ever synthetic eukaryotic genome. Synthetic genomes allow the genetic content of a cell to be fully designed in silico and then built in vivo, allowing widespread changes and new functions not feasible using existing physical gene editing techniques. This technical capability to create bespoke genomes programming organisms for specific tasks would have a wide range of applications - particularly in developing disease models, developing new therapeutics and converting industrial processes to sustainable alternatives. Unfortunately, our understanding of which genes would be needed to program desired cellular behaviour under different growth conditions is lacking. The current methods of determining what these minimal gene sets might be are slow, laborious and inadequate.

To overcome this, we have designed and synthesised a next-generation synthetic chromosome to allows us to randomly and indiscriminately delete different combinations of genes on a massive scale. During this project, the student will generate these deletions and sequence the resultant populations of genetically diverse cells en masse. We will then apply pangenomic bioinformatics techniques to this data and determine the contribution of each gene to cell viability in a range of conditions. The student will then test promising minimal gene sets to determine improved efficiency of growth and bioproduction. The project will not only greatly enhance our understanding of the relationship between gene content and cellular function, but will also lay down the foundation for bespoke synthetic genomes to be created for more efficient, predictable and safe biotechnology.