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The Erie Group

The Erie Group

Members of the Erie Group focus on using single molecule and biochemical methods to better understand the kinetics and thermodynamics of protein-nucleic acid interactions. Current single molecule techniques used in the lab include Atomic Force Microscopy (AFM) and Total Internal Reflection Microscopy (TIRM) techniques such as Fluorescence Resonance Energy Transfer (FRET). A major focus of our lab is the characterization of both the static and the dynamic protein-nucleic acid interactions that govern the overall repair specificity of mismatched or damaged DNA in prokaryotic and eukaryotic organisms. A few questions we are addressing include the following: How is mismatch repair initiated on some mismatches but not others? What properties of a damaged DNA substrate initiate apoptosis over mismatch repair? What roles do the mismatch repair initiation proteins, MutS and MutL, play in that separation of pathways? What are the structures/conformations of the multi protein-DNA complexes that control DNA repair? We are also characterizing a host of other protein-DNA interactions involved in DNA repair. There are projects within the group that would appeal to most areas of interest. Our group is composed of students from a variety of backgrounds and departments including chemistry, materials science, physics, and biophysics.

 

The Rubinstein Group

The Rubinstein Group

The research in the Rubinstein Group is in the field of polymer theory and computer simulations. The unique properties of polymeric systems are due to the size, topology and interactions of the molecules they are made of. Our goal is to understand the properties of various polymeric systems and to design new systems with even more interesting and useful properties. Our approach is based upon building and solving simple molecular models of different polymeric systems. The models we develop are simple enough to be solved either analytically or numerically, but contain the main features leading to unique properties of real polymers. Computer simulations of our models serve as an important bridge between analytical calculations and experiments.

 

Nitric Oxide-Releasing Glucose Biosensors

In vivo glucose biosensors have the potential to greatly improve the way diabetics manage their disease. Unfortunately, such devices do not function as intended, that is, reliably, after implantation due to inflammation and encapsulation due to the "foreign body response.” The Schoenfisch Group has for the last decade researched the benefits of materials that release nitric oxide, NO, to mitigate the foreign body response. In an article published in Analytical Chemistry, they describe the analytical performance benefits of a NO-releasing glucose biosensor percutaneously implanted in a swine model.

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Needle-type glucose biosensors were modified with NO-releasing polyurethane coatings designed to release similar total amounts of NO for either rapid or slower durations, and remain functional as outer glucose sensor membranes. Relative to controls, NO-releasing sensors were characterized with improved numerical accuracy on days one and three.

The clinical accuracy and sensitivity of rapid NO-releasing sensors were superior to control and slower NO-releasing sensors at both one and three days after implantation. In contrast, the slower/extended NO-releasing sensors were characterized by shorter sensor lag times in response to intravenous glucose tolerance tests versus burst NO-releasing and control sensors. Collectively, these results highlight the great potential for NO release to enhance the analytical utility of in vivo glucose biosensors. Initial results also suggest that this analytical performance benefit is dependent on the NO-release duration.

 

Electrocatalytic Carbon Dioxide Reduction

Accumulation of carbon dioxide in the atmosphere is considered a major contributor to climate change. Once captured, CO2 is a potentially useful feedstock if it can be converted into formate/formic acid, carbon monoxide, or more highly reduced hydrocarbon products. Electrochemical and photoelectrochemical CO2 reduction could become an integral part of an energy storage strategy with solar- or wind-generated electricity used to store energy in the chemical bonds of carbon-based fuels.

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The Meyer Group, in collaboration with the Department of Electrical and Computer Engineering at Duke University, published in JACS, reports on how Nitrogen-doped carbon nanotubes are selective and robust electrocatalysts for CO2 reduction to formate in aqueous media without the use of a metal catalyst. An overlayer of polyethylenimine (PEI) functions as a cocatalyst by significantly reducing catalytic overpotential and increasing current density and efficiency.

 

Ivy Carroll ACS Fellow

Dr. F. Ivy Carroll, member of Carolina Chemistry's External Advisory Board, has been recognized by the American Chemical Society as a 2014 ACS Fellow. He is honored for his contributions to science, including the design and development of a diagnostic agent for Parkinson's disease and compounds as potential treatments for cocaine and nicotine addictions and other central nervous system disorders. He is also recognized for his long service to ACS.

Dr. Ivy Carroll

Dr. Carroll is a Distinguished Fellow in medicinal chemistry with RTI International, which he joined in 1960. He has published more than 440 peer-reviewed publications, 34 book chapters, 43 patents, and more than 20 current patent applications. Among his many awards and recognitions are the 2010 North Carolina Award for Science, and the 2010 National Institute on Drug Abuse Public Service Award for Significant Achievement.

 

Cerebral Blood Flow

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. In an article published in the Journal of Cerebral Blood Flow & Metabolism, researchers in the Wightman Group investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis, vBNST, of an anesthetized rat by measuring O2, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O2 were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O2 levels followed by a brief dip below baseline.

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Supporting the role of a hyperemic response, the O2 increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O2 is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O2 influx in a deep brain region.

 

Improved Diesel Process

Typically, diesel fuel is made from crude oil, but scientists can make high-grade diesel from coal, natural gas, plants or even agricultural waste, using a process called Fischer-Tropsch, or FT. Just about any carbon source is an option. FT Diesel is the ideal liquid transportation fuel for automobiles, trucks and jets. It's much cleaner burning than conventional diesel, and much more energy efficient than gasoline. But, FT Diesel is expensive to make and generates lots of waste.

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With support from the National Science Foundation, NSF, and its Center for Enabling New Technologies Through Catalysis, CENTC, chemists from around the United States, including professor Maurice Brookhart from Carolina, are working together to improve the cost and energy efficiency of alternative fuels. CENTC scientists have invented and patented, and are bringing toward commercialization, catalysts that will convert light hydrocarbons into FT Diesel, improving the process, whether it's diesel made from traditional sources, such as oil, or alternative sources, such as biomass.

NSF: Miles O'Brien, Science Nation Correspondent; Ann Kellan, Science Nation Producer

 

Massively Parallel Clonogenic Screening

Wnt/β-catenin signaling is of significant interest due to the roles it plays in regulating development, tissue regeneration and disease. Transcriptional reporters have been widely employed to study Wnt/β-catenin signal transduction in live cells and whole organisms and have been applied to understanding embryonic development, exploring oncogenesis and developing therapeutics. Polyclonal heterogeneity in reporter cell lines has historically been seen as a challenge to be overcome in the development of novel cell lines and reporter-based assays, and monoclonal reporter cell lines are commonly employed to reduce this variability.

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Published in Integrative Biology, researchers in the Allbritton Group describe how A375 cell lines infected with a reporter for Wnt/β-catenin signaling were screened over short (<6) and long (>25) generational timescales. To characterize phenotypic divergence over these time-scales, a microfabricated cell array-based screen was developed enabling characterization of 1119 clonal colonies in parallel. This screen revealed phenotypic divergence after <6 generations at a similar scale to that observed in monoclonal cell lines cultured for >25 generations. Not only were reporter dynamics observed to diverge widely, but monoclonal cell lines were observed with seemingly opposite signaling phenotypes. Additionally, these observations revealed a generational-dependent trend in Wnt signaling in A375 cells that provides insight into the pathway's mechanisms of positive feedback and self-inhibition.

 

 

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