THE SHAFFER LAB - UNIVERSITY OF KENTUCKY

We are developing powerful tools that enable dissection of type IV secretion system (T4SS) apparatus assembly and characterization of genetic pathways that regulate T4SS function. These molecular scalpels offer temporal control and reversibility, providing major advantages over traditional genetic techniques. In collaboration with synthetic chemists, we aim to develop robust chemical scaffolds that selectively disarm virulence mechanisms in diverse bacterial pathogens.

We have a limited understanding of how the dynamic T4SS nanomachine assembles in response to target cell docking. Our lab uses biochemical approaches, advanced super-resolution microscopy, and genetics to understand how components of the T4SS interact to facilitate movement of molecular cargo from the bacterium to the host cell. We aim to understand molecular mechanisms underpinning effector delivery and to determine the role of novel extracellular features associated with these diverse surface organelles. Defining how these systems assemble and function will allow us to harness versatile T4SS machinery for the targeted delivery of biological substrates.

How does translocated microbial cargo interact with components of the host cell? Our lab studies how pathogens build external structures that interact with host cell surfaces to trigger the delivery of substrates into specific cellular compartments. We use in vitro models of host-pathogen interaction to understand how injected molecular cargo stimulates host defense systems mounted in response to pathogen breach. These studies provide insight into mechanisms of bacterial stealth and highlight how evolution has guided protein mimicry and co-option to drive microbial occupation of diverse microenvironments.