(492g) Genome-Scale Engineering of Lactococcus Lactis for Probiotic Outcomes

Humans have long reaped the benefits of probiotics via food fermentation with lactic acid bacteria. In this talk, I will discuss efforts in our research group to engineer the lactic acid bacterium Lactococcus lactis for improved probiotic outcomes. For example, besides its use in fermentation and in industry as a lactic acid producer, L. lactis has also been engineered for delivery of therapeutic proteins in vivo in the gut environment. We seek to use the toolbox of synthetic biology to expand the capabilities of this organism as an engineered probiotic. Our approach takes two routes: (1) Increasing the efficiency of genome engineering using the versatile CRISPR-Cas9 technology in this organism and (2) Discovery of genes and pathways that contribute to complex phenotypes by creation of genome-scale libraries and selection for desired phenotypes such as chemical tolerance and protein secretion. We also discuss the use of prebiotics to synergistically improve outcomes by encouraging lactococcal growth in complex environments. Increased throughput of genome engineering and identification of genomic targets will broaden the range of uses of this already food-safe organism for both industrial and human health purposes.