Controlling Evolutionary Dynamics of Antibiotic Resistance

Speaker: Prof. Erdal Toprak
Affiliation: University of Texas Southwestern Medical Center

Abstract:  Antibiotic resistance is a growing public health problem. Prolonged treatment times due to drug resistant pathogens increase human suffering and health care costs. Understanding the genetic changes responsible for elevated drug resistance can inform novel strategies for combating drug resistance. In this seminar, I will first introduce a novel automated microbial selection device, the “morbidostat”, which we developed to study the long term evolution of antibiotic resistance. Following that, I will summarize our recent work where we synthetically construct and analyze all possible combinations of antibiotic resistance conferring mutations. Our results show that resistance evolves through an extremely rugged adaptive landscape with direct and indirect paths leading to distinct resistance peaks. High-order interactions between adaptive mutations create this highly rugged fitness landscape, where the distributions of most mutations’ effects are indistinguishable from increasing or decreasing resistance by flipping a coin. Finally, I will summarize what we learned from evolving antibiotic-resistant bacteria in our lab and how we used these findings for developing a novel antibiotic.

Biography:  Erdal Toprak is an assistant professor at the University of Texas Southwestern Medical Center and the Southwestern Medical Foundation Endowed Scholar in Biomedical Research. Erdal Toprak received his Ph.D. in Computational Biology and Biophysics in 2007 from the University of Illinois at Urbana-Champaign where he studied motility mechanisms of molecular motor proteins with Paul R. Selvin. He then moved to Roy Kishony’s Lab at Harvard Medical School as a postdoctoral research fellow where he developed the Morbidostat for studying evolution of antibiotic resistance. The Toprak Lab investigates genetic and molecular basis of antibiotic resistance by using a range of methodologies for developing novel strategies that can stop and reverse evolution of resistance. The Toprak Lab also develops new technologies for rapid antibiotic sensitivity testing and pathogen detection.

For more information, contact Prof. Aydogan Ozcan ()

Date/Time:
Date(s) - Feb 05, 2020
1:00 pm - 2:30 pm

Location:
E-IV Faraday Room #67-124
420 Westwood Plaza - 6th Flr., Los Angeles CA 90095