Membrane transport proteins – channels and energy-coupled pumps – are the molecular gatekeepers of the cell. These proteins import vital nutrients and export 
dangerous toxins. We want to understand how these proteins work on a structural and molecular level. We are especially interested in how these proteins help microorganisms cope with environmental stressors. Humans have introduced antiseptics, PFAS, pharmaceuticals, and pollutants to the environment over the last hundred years. Understanding how bacteria resist these challenges will provide new leads for antimicrobial development.
We think that it is important to combine information about structure, protein dynamics and function, and cellular physiology to really understand a system. Therefore, our lab uses techniques including: cryo-EM, biochemistry, single molecule biophysics, X-ray crystallography, microbiology, and evolutionary analysis.
We have funding from the NIH and NSF and positions available! Here is a sampling of some of the lab’s current projects:
Cryo-EM and structural analysis of membrane proteins. Ultimately, we want to know how these proteins work on a molecular level. The panel at left shows a cryo-EM map of a fluoride exporter in complex with an inhibitory drug.
Fluoride resistance in oral pathogens. Microbes associated with oral health resist fluoride using different mechanisms than bacteria associated with dental disease. The figure at left shows fluoride bound to a bacterial fluoride channel that our lab discovered. We are developing antibiotics that work together with fluoride to kill oral pathogens. We are also interested in the role of fluoride resistance in PFAS degradation.
Mechanisms of bacterial resistance to household antiseptics, pharmaceutical metabolites, and other chemicals that accumulate in the environment.
The figure at right shows a model of the E. coli drug exporter from the Small Multidrug Resistance (SMR) protein family in complex with the active agent in Lysol. Our lab uses evolutionary analysis, structural biology, and single molecule biophysics to understand the molecular basis of substrate polyspecificity. The figure below shows a single molecular FRET trace of the transporter dynamically moving between cytoplasmic- and extracellular-facing states.
Molecular evolution of novel protein folds and functions. We use high throughput mutagenesis, next generation sequencing, and phylogenetics to understand the evolutionary forces that have shaped membrane protein fold and function.
