Calendar

Introduction to the semester’s seminar series, by Dr. Young-Ok You.

Chem 490/790

“The Sphingosine-1-phosphate pathway: Sphingosine kinase as a drug target”

Dr. Webster Santos (Virginia Tech)

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P1–5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer, fibrosis, inflammation, neurodegenerative diseases, and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this presentation, I will discuss our efforts in inhibiting SphK through extensive medicinal chemistry campaigns. The activity of inhibitors in mice as well as their therapeutic implications will be discussed.

Please email Dr. You at yyou@gmu.edu if you’d like to meet the speaker.

“Medicines from bacterial resource and its impact on human health”

Dr. Young-Ok You (GMU)

Please email Dr. You at yyou@gmu.edu if you’d like to meet with her.

“Reaxys chemistry database”

Dr. Irakli Samkurashvili (Elsevier)

Please email Dr. You at yyou@gmu.edu if you’d like to meet the speaker.

“Voltage sensor activation in the Hv1 proton channel: structural and mechanistic insights are revealed by voltage clamp electrophysiology and molecular dynamics simulations.”

Dr. Ian Ramsey (VCU)

Please email Dr. You at yyou@gmu.edu if you’d like to meet the speaker.

By: Dr. Monique van Hoek
Antibiotic resistant bacteria are a growing threat. We need new antimicrobial agents and new approaches to defeat deadly bacterial infections. My lab has been looking to nature for new anti-bacterials. Our BioProspector system can find anti-bacterial peptides in very small samples of blood. In fact, we have found new anti-bacterial peptides in the blood of Alligators and Komodo dragons. Some of these peptides kill important antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus or MRSA. I will explain what the BioProspector system is, how we identified these peptides from Komodo dragons, and how some of these peptides can kill dangerous bacteria.

Also speak one-on-one with biochemist Dr. Barney Bishop who is co-investigator on this project.

RSVP

6:00PM: Doors open, food and beverages available
7:00PM-7:30PM: Scientific Discussion
7:30PM-7:45PM: Q&A
7:45PM-8:30PM: Meet the Scientist and Networking Reception

“Bivalent Ligand Approach to Understand the role of Putative Mu Opioid Receptor and Chemokine Receptor CCR5 Heterodimers in NeuroAIDS”

Dr. Yan Zhang (VCU)

Please email Dr. You at yyou@gmu.edu if you’d like to meet the speaker.

Characterization of the Acid-base Properties of Selected Humic Substances and Model Compounds

Determination of the surface density of acidic functional groups and the magnitude of pK_a ’s of carboxylic and phenolic functional groups is a first step in characterizing acidity, ion exchange capacity, and charge accumulation properties in humic substances (HS). Potentiometric titration was used to determine the fundamental acidic properties of natural HS and selected model HS to better assess the role structure plays in carboxyl and phenol group dissociation.

The model compounds were simple benzofuran (C₈H₆O) derivatives, a common structural motif in HS. The pK_a and K_a values of the model compounds were evaluated accurately and precisely, thus useful to determine structural variations in dissociation. In order to determine the concentration and conditional pK_a’s of the ionizable sites, a nonlinear method for fitting acid-base potentiometric titration data, was applied to the HS titrated for this study. Each HS was assumed as a mixture of monoprotic acids in the model.

Besides Thermodynamics, What Other Factors Are Controlling Mineralization and Weathering at Near-Surface Conditions?

Henry Teng (George Washington University)

Please email Dr. You at yyou@gmu.edu if you’d like to meet the speaker.

Natural process of mineral formation and dissolution at near-surface conditions are subject to various effects ranging from that of aqueous speciation to biological participation.  As such complications arise for laboratory investigations of mineralization and weathering when thermodynamicd is considered the only driving force.  Two case studies, one is solution chemistry effect on crystallization and the other microbially mediated dissolution, will be discussed in this presentation to highlight the complexity.

For mineralization, the classical approach states that the net growth rate of mono-molecular layers (ie, step velocity) is determined by the difference between fluxes of species attaching to and detaching from kinks along step edges.  Such treatment leads to the development of the widely accepted understanding that step velocity depends solely on solution supersaturation.   Yet, literature data from numerous cases argued strongly against this supposition.  In this study, we conducted a series of in situ AFM experiments to interrogate the effect of solution chemistry parameters on step kinetics using calcite as a model system.  We found step kinetics were strong affected by solution pH, ionic strength SI, and the [Ca2+]/[CO32-]  ratio, and the impact differs in different cleavage directions. These observations suggest that, although supersaturation is the driving force for aqueous phase crystallization, solution chemistry plays critical roles in controlling the actual growth rate and needs to be taken into consideration in kinetic studies of crystallization.

For bio-weathering, complications are often associated with cell-mineral interfacial reactions because of physiology changes in microbes once becoming surface-bound and also because of the involvement of biomechanical forces in the case of fungal dissolution.  In this study we examined lizardite [Mg3Si2O5(OH)4] dissolution by a native fungal strain in bulk media and at interface through determining the total metal release in culture, the pH local to surface-bound cells, and the material composition and structure beneath cell-colonized surfaces.  We found that (1) cellular dissolution proceeds by a mechanism fundamentally different from that at the mineral-water interface, (2) only attached cells release siderophores, and (3) biomechanical forces of hyphal growth are indispensable for fungal weathering and strong enough to breach the mineral lattice.  These results strongly suggest that fungal cell-promoted interfacial dissolution may have been significantly underestimated in the current understanding of microbial geochemistry.