Quantifying the Transition from Non-Genetic to Genetic Drug Resistance

*To request access to the videoconference, email dsivak@sfu.ca

Synopsis

Antimicrobial (drug) resistance poses a major threat to health care systems and economies worldwide; it has been predicted that, if unmitigated, drug resistance could result globally in the death of 10 million people per year and have a cumulative economic cost of 100 trillion USD by 2050. Recently, it has been established that non-genetic mechanisms play an important role in the development of acute drug resistance. However, the role of non-genetic drug resistance (resistance that does not result from a change in the DNA sequence) in the establishment of longer-term genetic drug resistance (resistance acquired from a DNA mutation) is still speculative. We are using mathematical/computational modeling together with synthetic biology to quantify the transition from non-genetic to genetic drug resistance. We are also performing microbial evolution experiments on genetically engineered yeast to investigate the effects of fluctuating drug environments on the evolution of drug resistance. In this seminar, an overview of the tools and methods used in this research, along with preliminary simulation and experimental data, will be presented. Overall, this research aims to advance our fundamental understanding of life, develop more effective “evolution proof” antimicrobial treatments for patients with drug-resistant infections, and engineer more robust gene networks for real-world applications.