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Dr. Tae-Hee Lee of Penn State University will be presenting a seminar titled Single Molecule Studies of Nucleosome Structure and Dynamics.

Abstract: The nucleosome is the fundamental packing unit of the eukaryotic genome. The structure and structural dynamics of the nucleosome are at the core of the mechanisms of gene regulation and maintenance. We studied the structure, structural dynamics, and assembly of nucleosome core particles and how these properties are altered by various epigenetic modifications based on single molecule fluorescence measurements. Our study revealed that these modifications induce changes in the nucleosome core particles that may directly or indirectly contribute to gene regulation activities. Our study demonstrates how single molecule methods can fill the niche not covered by the conventional structural biology tools.

Refreshments will be served at this event.

Faculty Host:  Dr. Chris Richards

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Bidhya Maharjan of the University of Kentucky will be presenting a seminar titled Ferrocene-Fused Derivatives of Polyacenes, Tropones and Thiepin.

Faculty Advisor: Dr. John Selegue

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Dr. Rajeev Misra of Arizona State University will be presenting a seminar titled In vivo Investigation of Bacterial Multidrug Efflux Pumps. 

Abstract: Multidrug resistance among human bacterial pathogens remains a grave social concern. A common cellular mechanism bacteria frequently employ is the efflux of antibiotics from the cell; resistance develops when the rate of drug efflux across the membrane exceeds that of drug influx. One of the most extensively studied multidrug efflux systems of the Resistance-Nodulation-Division (RND) family comprises of the AcrA, AcrB and TolC proteins of Escherichia coli. Fine structural analyses have provided deeper understanding of how drugs are captured and pushed through the AcrB pump protein. However, much remains to be learned as to how the tripartite pump assembles to extrude drugs from AcrB to outside the cell. I will discuss our efforts to gain a better understanding of the AcrAB-TolC pump assembly in vivo.

Due to their high clinical relevance, inhibitors have been sought to reduce or abolish the activity of multidrug resistant efflux pumps. Phenylalanine arginine β-naphthylamide (PAβN) was one of the first lead compounds that showed a potent inhibitory activity against a number of RND pumps, including AcrB. However, the conclusion that PAβN acts principally as an efflux pump inhibitor was questioned by several recent publications. We have attempted to resolve this controversy by employing strains constitutively expressing AcrAB or a homologous AcrEF efflux pumps. The employment of a modified real-time efflux assay allowed for the first time a clear distinction between the efflux pump-inhibiting activity of PAβN and membrane-permeabilizing action of polymyxin B nonapeptide (PMBN). It was determined that at low concentrations, PAβN acts mainly as an inhibitor of the AcrAB and AcrEF efflux pumps. However, at high concentrations, PAβN in the efflux-proficient background not only inhibited the efflux pump activity but also destabilized the membrane. The effects of PAβN on membrane integrity are compounded in cells unable to extrude PAβN.

Refreshments will be served at this event.

Faculty Host: Dr. Yinan Wei

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The seminar has moved to CP-220.  



Dr. Franz Geiger of Northwestern University will be presenting a seminar titled Direct Views of the Nano-Bio Interface.

Abstract:  The tendency of proteins, lipids, and other biological species to form coronas around nanoparticles has been put to great use for promoting or inhibiting cellular uptake of engineered nanomaterials. This situation raises the question whether lipid coronas can form spontaneously at the interfacial region between a nanomaterial and a biological membrane, i.e. the nano nano-bio interface, and thereby regulate cellular uptake. Here, we describe the interaction of a well-characterized set of ligand-coated nanoparticles with lipid bilayers of varying chemical composition, the gram-negative bacterium Shewanella oneidensis, and a multicellular organism, the water flea Daphnia magna. Using nanoparticle- and membrane-specific data from microscopy, spectroscopy, and mass measurements, we determine that particles coated with cationic polyelectrolytes disrupt largely zwitterionic bilayers under electrostatically attractive conditions while all other particle-ligand combinations surveyed leave the bilayers intact. Moreover, we report that bilayer disruption coincides with lipid corona formation around the particles and propose this mechanism as the molecular basis for a nanoparticle-specific effect that lowers the survival rate of D. magna when they are exposed to particles wrapped in cationic polyelectrolyte.  Finally, we demonstrate the key role of lipopolysaccharides in protecting S. oneidensis from nanoparticle uptake.

Refreshments will be served at this event.

Faculty Host: Dr. Marcelo Guzman