New paper in PLOS Biology

New paper in Nature Communications

New paper in PLOS Biology

Evolution of Antibiotic Resistance
Emergence of antibiotic resistance is an ever-growing public health problem in all countries on our planet regardless of their development statuses. For example, Methicillin-resistant Staphylococcus aureus (MRSA) infections kill more people annually in the United States than HIV. In our lab, benefiting from long term evolution experiments and whole genome sequencing, we develop novel strategies to use antibiotics more efficienty for slowing down the evolution of antibiotic resistance.
Genetic and molecular constraints that potentiate evolution of antibiotic resistance.
Pathogenic bacteria acquire resistance conferring genetic changes in order to overcome the inhibitory effects of antibiotic molecules. Being able to predict genetic trajectories that lead to resistance is potentially useful for developing novel antibiotic therapies. However, predicting the evolutionary trajectories is often quite difficult due to complex epistatic interactions between resistance conferring genetic changes. In order to reveal constraints that dictate plausible genetic trajectories that lead to drug resistance, we synthetically construct and phenotype enzymes that carry all combinatorial sets of resistance conferring mutations. We also characterize mutant enzymes’ catalytic activities via biochemical assays for revealing the trade-offs between enzyme biochemistry and resistance.
Using synthetic biology for making novel antimicrobial biomolecules.
Organisms that produce antimicrobial molecules have been successfully using these molecules as chemical weapons and chemical signals for millions of years. Therefore, learning how optimal antimicrobial molecules are is important to design new drugs. Using a systems biology approach, we construct libraries of antimicrobials and characterize their killing activities. We aim to synthetically engineer antimicrobial biomolecules that can potentially be used for clinical purposes.