THE SHAFFER LAB - UNIVERSITY OF KENTUCKY

Chemical Tools to Study Secretion System Biogenesis and Function

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 a major advantage over traditional genetic techniques. In collaboration with medicinal chemists, we aim to develop robust chemical scaffolds that selectively disarm virulence mechanisms in diverse bacterial pathogens.

Architecture and Topology of Molecular Machines

We have a limited understanding of how dynamic T4SS nanomachines assemble in response to docking with target cells. 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 the 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 the machinery for the targeted delivery of biological substrates.

Microbial Interactions with the Host

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 injection of substrates into specific cellular compartments. We use in vitro models of host-pathogen interaction to understand the fate of these effector molecules, and to investigate the host defense 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.

Carrie L. Shaffer, PhD

Assistant Professor

Department of Veterinary Science

Department of Microbiology, Immunology, and Molecular Genetics

Department of Pharmaceutical Sciences

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