Making Discoveries that Make a Difference
[display-posts category=”research”]

Analytical

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Dr. Abul Hussam: “I have been involved in the development electroanalytical techniques for the study of toxic species in the environment. We are particularly interested in the chemistry of arsenic in groundwater and the development of inexpensive arsenic filters.

First, we have developed a field technique to measure parts-per-billion level of arsenic species in groundwater. Second, we have devised a simple method to purify groundwater from toxic arsenic species. More than 10,000 such filters are in use in Bangladesh and continue to provide more than a Billion liter of clean drinking water.

In addition, we are actively engaged in the development of hardware and virtual software for electroanalytical engines (reagent generator and sensor) to be used with ‘lab-on-chip’ platform. We have also extended the use of electrochemical techniques to understand the diffusion behavior and electron transfer kinetics of lipophilic redox species in organized media such as micelles and microemulsions.

To complement these studies we have built a high precision headspace gas chromatograph to study the partition behavior of volatile species in complex micelles and microemulsions.”

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Dr. John Schreifels: “My laboratory works on problems associated with the solid – gas interface. We study molecular events occurring in the top few atom layers of solid surfaces (thickness levels of about 1/10000 the thickness of a human hair).

Recently, we studied the interaction of fuel additives with stainless steel surfaces. Certain compounds (called metal deactivators, MDA) are added to bulk fuel to eliminate fuel degradation during long term storage under ambient conditions. It turns out that fuels also form dark thick deposits on injectors of jet engines during operation. The temperature in the injector is much higher, which means the deposition rate is much higher than in the bulk fuel. These deposits can cause catastrophic failure of the engine.

The presence of MDA can reduce this effect. We studied the fundamental interactions of the compound with stainless steel in our instrument under ultra – high –vacuum conditions. The vacuum insured that we were studying only the interaction of the compound with the stainless steel surface. We found that the compound broke into smaller fragments upon initial exposure of the surface to the compound.

There were several new compounds generated in addition to the original compound that might have been the cause of the reduced deposition of residues on the surface. In fact because of the temperature at which each of these compounds desorb, from the surface we believe the new compounds may very well be responsible for the reduced rate of deposition.

Using the insights from this study, we will continue to deposit other compounds with chemical structures similar to the compounds detected on the surface to try to understand how to produce an improved effect. Additionally, we are studying the adsorption of compounds that are used to reduce the extent of corrosion.

Finally, our studies have involved metallic surfaces and how they interact with compounds to produce new compounds; these metal surfaces are often called catalysts and are used extensively in the chemical industry.”

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Biochemistry

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Dr. Barney Bishop: “In my laboratory, we are interested in applying peptide/protein engineering principles to investigate biomolecules and their function. The rampant increase in the incidence of multi-drug resistant bacteria and the threat of bioterrorism necessitate new approaches to preventing and treating infection.

Higher organisms produce a complex host of molecules that they use to combat infection and invading microbes. In these defensive mechanisms, peptides and proteins consistently stand out as critical elements. Therefore, we are interested in studying the biophysical properties of these molecules and the varied antimicrobial mechanisms employed by them.

As a model system, we are looking at the defensin family of peptides, whose members demonstrate antimicrobial activity against a broad spectrum of pathogens including bacteria, fungi and viruses. We believe that such studies will provide valuable insights into strategies for combating bacterial and viral infections, and we intend use this information in the design of novel therapeutic agents and biomaterials.”

Bishop Group Website

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Dr. Robin Couch
The Couch lab is researching several aspects of developments of MEP pathway inhibitor antibiotics, small molecule metabolomics, biosensor/electronic nose, and chemoprevention of Alzheimer’s disease.

The increasing prevalence of antibiotic resistant strains emphasizes the need for continued development of new antibiotics with novel mechanism of action. Many human pathogens exclusively use the methylerythritol phosphate (MEP) pathway, making it an excellent target. To facilitate MEP pathway inhibitor development, my lab has cloned, expressed, and enzymatically characterized several MEP pathway enzymes. We are iteratively deriving structure-activity relationships and performing mechanism of inhibition assays to guide the development of rationally designed synthetic inhibitors of these enzymes.

We are also using state-of-the-art metabolomics techniques to evaluate small molecule metabolites present in biological samples, including feces. We are currently using both GC-MS and LC-MS in our analyses to examine fecal volatile organic compounds (VOCs). We discovered that the current technologies were inadequate to facilitate a proper headspace solid phase microextraction-based (hSPME) metabolomics analysis of biological samples. We developed and patented a device that enables these analyses, and coined the term “simulti-hSPME” to describe our optimal process of using multiple sorbent types to simultaneously extract VOCs of diverse chemistries from a sample. We are also using our newly developed simulti-hSPME for the rapid and minimally invasive detection of biothreat-relevant microbes (“electronic nose”).

We are applying our small molecule and protein expertise to determine the signal transduction mechanism underlying the ability of select small molecules to induce nerve growth factor release from glial cells. Nerve growth factor keeps neurons alive, and thus has promise for the chemoprevention of Alzheimer’s Disease. Using cultured human glial cells, we have utilized reverse phase protein microarrays to generate temporal maps of signal transduction protein activation, and we are now validating the involvement of these proteins/pathways using pathway specific agonists and antagonists.

Couch Group Website

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Dr. Young-Ok You: “My overall research goal is the understanding the fundamental mechanism of PKS biosynthase and the application of the knowledge to develop novel compounds for treatment of disease. Multi-disciplinary approaches such as molecular biology, microbiology, organic synthesis, analytical chemistry and bioinformatics are employed in our lab.

The current on-going research is largely in two directions. The first is enzymology of trans-AT PKS in order to understand the fundamental mechanisms of this new class of PKS. These include the split-module system, condensation-incompetent ketosynthase domain(s), protein-protein interactions, and enzymology of the protein complex. I am expecting this research will help to fill the current gap of knowledge in the trans-AT PKS system and further used to decipher orphan trans-AT PKS systems which will lead to the discovery of new PKS compounds.

The second direction is to produce non-immunosuppressant FK506 analogues by synthetic and bioengineering approaches. FK506 is an immunosuppressant which is biosynthesized by PKS-NRPS in several Streptomyces strains. Clinical, pre-clinical and biochemical evidences shows that FKBPs are overexpressed in diseases such as lung fibrosis, prostate cancer and Alzheimer’s disease. However the systematic immune suppressant activity of FK506, the original ligand of FKBPs, prevent its use for the treatment of diseases. Hence, FK506 analogues without immune suppression are needed. Production of non-immunosuppressant FK506 analogues by semi-synthesis, genetic manipulation of the biosynthetic machinery of FK506 is under the investigation.  In addition to that, discovering novel FKBPs inhibitors by bioinformatics approach from newly sequenced bacterial genomes is underway.”

 

Environmental

Dr. Gregory Foster: “Students in the Foster research laboratory investigate the sources, reactions and transport of contaminants in the aquatic environment. Currently, we have two ongoing lines of active research. The first involves determining the amounts and sources of polychlorinated biphenyls (PCBs) in storm runoff in the Anacostia River, a tributary of the Potomac River that runs through Washington, DC.

PCBs are persistent, carcinogenic organochlorine contaminants that are thought to adversely affect both human and environmental health. The Anacostia River is one of the three most heavily contaminated PCB regions in the Chesapeake Bay watershed, where the highest sedimentary PCB concentrations have been reported to date. We are aiding in a massive clean up of PCBs in the Anacostia River. Storm flow runoff is the primary mode of input of PCBs in the Anacostia River, and storm flow inputs must be characterized to design effective, long-term clean up strategies.

The second line of research is in determining the inputs of pharmaceutical and personal care chemicals in the Potomac River. Over 32 wastewater treatments plants in the metropolitan DC region release pharmaceutical chemicals through wastewater discharge, and some of these biologically active chemicals are severely impairing reproductive development in fish species by serving as estrogen mimics (as recently reported in the Washington Post). We are investigating the nature of pharmaceutical chemical inputs and potential estrogenic effects in aquatic organisms.”

Foster Group Website

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Organic

Dr. Robert Honeychuck: “We are in the business of synthesizing small molecules which either are in bacteria, or look like those in bacteria. Currently, these include molecules which bind iron in living bacterial organisms. In the long term we would like to take these molecules and attach them to inert surfaces so that they could be used in iron sequestering or detection.

In addition, it might be possible to mimic the environment in bacteria where the molecules reside, in order to determine their structure and function (why they are there). More complete knowledge of the function of the natural molecules in bacteria may provide us with methods of slowing the growth of bacteria on food and in host humans, and might also provide new ways to bind metals in humans and render those metals inert or harmless.

We divide our time into three general parts: making, purifying, and proving. The making of these compounds in the laboratory is the part where we use imaginative methods of putting molecular pieces together. Our attention then turns to the sometimes endless task of obtaining clean samples of these compounds, free of items which tend to obscure their properties. When we have clean compounds we can then provide convincing evidence that we have made what we said we made.

Part of what makes the whole process exciting is the collaborative nature of it: the bacterial connection is through a group in the GMU School of Systems Biology.”

Honeychuck Group Website

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