Professor J.P. Gerdt (Indiana University)

Title: Chemical Regulation of Bacterial Immune Systems

Abstract: Bacteria get "sick" too. A substantial fraction of our world's bacteria are killed each day by viruses called bacteriophages (phages). These viruses also naturally transmit genes that shape microbial communities across the planet. Furthermore, these natural predators are promising alternatives to antibiotics in the clinic, in agriculture, and in other industries. However, bacteria have evolved myriad immune systems that afford resistance to phages. These immune systems are likely shaping the composition of microbiomes and rendering phage therapies ineffective. Until now, these immune systems have not been probed with chemical inhibitors. My laboratory has begun to fill this void with newly discovered small molecule inhibitors of several anti-phage immune systems. I will discuss our inhibition of several TIR domain-containing immune systems (Types I and II Thoeris, and SpbK). The inhibition mechanisms will be discussed, as well as how the inhibitors can be used to promote the efficacy of phage therapies, revive the infectivity of phages that are repressed to low levels in a population, and enable the activation and spread of prophages. I will also show beyond synthetic small molecule inhibitors how natural products may already be influencing the sensitivity of bacteria to phages in diverse microbiomes.

Biography: J. P. Gerdt earned a B.S. in Chemistry (summa cum laude) in 2008 from the University of Illinois at Urbana–Champaign and a Ph.D. in Chemistry in 2014 from the University of Wisconsin–Madison (with Helen Blackwell). After 5 years of postdoctoral research on chemical signaling in microbial eukaryotes at Harvard Medical School (with Jon Clardy), Dr. Gerdt started his independent career in the Department of Chemistry at Indiana University in 2019. By integrating analytical, organic, and biological chemistry with microbiology and cell biology, the Gerdt lab uncovers the molecules that shape microbial symbioses. The two biological systems his lab studies are (1) protists that help to reconstruct the evolutionary pathways that formed multicellular animals and (2) bacteriophage viruses that kill pathogenic bacteria. Dr. Gerdt is a recipient of the NIH Maximizing Investigators' Research Award (2020), NSF CAREER Award (2021), Camille-Dreyfus Teacher-Scholar Award (2024), and Indiana University Outstanding Junior Faculty Award (2026).