Research
The Tarnopol Lab studies protein toxin evolution at the host-pathogen interface.
Toxic proteins sit at the heart of host-pathogen interactions. They are deployed by both hosts and pathogens and evolve rapidly. We aim to understand how protein toxins evolve and how they shape species co-evolution across levels of biological organization.
To accomplish this, we use naturally occurring insect-Bacillus thuringiensis (Bt) model systems to study the impacts of toxin evolution from the level of the protein to the level of the whole organism. Bt encodes myriad proteinaceous toxins, which comprise the most economically important toxin family due to their widespread use in pest management. Bt toxins target diverse protein receptors, which in turn evolve resistance. Our research is grounded in experimental and evolutionary genetic approaches but pulls from diverse areas of biology.
What are the molecular rules governing toxin specificity?
Despite their widespread use in pest management, little is known about how Bt toxins act with extreme specificity towards target pest insects without harming beneficial insects or humans. We are using high-throughput mutagenesis techniques to survey toxin-receptor interactions in order to elucidate the molecular rules driving Bt toxin specificity at the amino acid level.
How do toxins contribute to pathogenesis?
The role of Bt toxins in promoting B. thuringiensis pathogenesis is controversial. Bt is a poor colonizer of insects and its contribution to septicemia is unclear. We leverage the laboratory tractability of Drosophila melanogaster to dissect the impact of Bt toxins in potentiating a pathogenic lifestyle.
How does organismal context shape protein evolution?
Toxic proteins occupy a precarious biological position: By targeting conserved cellular features, they can potently inhibit their targets, but also run the risk of autotoxicity towards the producer. This is particularly salient for toxins deployed by animal innate immune systems, which must target a wide array of pathogens without harming the host. We are developing high-throughput mutagenic strategies in Drosophila melanogaster to probe the impacts of innate immune protein evolution on organismal fitness.