Nathan Schmidt, Ph.D.
University of California, San Francisco
“Molecular design principles from host defense peptides and bacterial stress sensors”
In this seminar I will describe how a molecular understanding of proteins involved in host-pathogen interactions can be used to establish design rules for engineering biomaterials that impact biomedical sciences. Antimicrobial peptides (AMPs) comprise an important part of the host defense as direct microbicides from membrane permeabilization and modulators of the immune response. I will explain how the selective generation of disruptive curvatures in microbial membranes provides AMPs with a broad mechanism to target bacteria, and how this mechanism can be multiplexed with additional roles in host defense that can sometimes contribute to autoimmune diseases. Through co-evolution with their hosts, bacteria have developed two-component systems that sense AMPs and orchestrate phenotypic changes that reduce susceptibility and trigger virulence factors. I will explain how modularity in the design of the sensor component, the histidine kinase, provides these proteins with a generic structural mechanism to switch signaling states and maintain bistability. The potential application of these molecular design principles toward antibiotics, immunotherapies, and engineering proteins with unprecedented functions will be discussed.
Nathan Schmidt is a postdoctoral fellow in William DeGrado's lab at the University of California, San Francisco studying bacterial two-component systems and protein design. He is interested in understanding the structural mechanism for signal state switching in histidine kinases, and using this knowledge to engineer biomaterials. Nate earned his PhD with Gerard Wong at the University of Illinois, Urbana-Champaign studying the interaction of antimicrobial peptides with biomembranes and establishing design rules for membrane-active antibiotics.