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 You Group focuses on the synthesis and characterization of novel multifunctional materials for a variety of applications, predominately in electronics and photonics. Challenges to be addressed include, for example, can a 10% solar cell be made through organic materials? Can single molecules serve as the fundamental unit for electronics and spintronics? Group members are working tirelessly to answer these questions by applying interdisciplinary approaches, including organic and polymer synthesis, surface chemistry, nano-patterning, device fabrication, and physical properties characterization using state-of-the-art instrumentation.
Dr. Linda L. Spremulli, Professor of Chemistry at the University of North Carolina at Chapel Hill, has been selected as the UNC-CH recipient of the 2012 Board of Governors Award for Excellence in Teaching.
Teaching is the University's primary obligation and proudest accomplishment of its faculty. In 1993, the Board of Governors established this award with the following resolution: "To underscore the importance of teaching and to encourage, identify, recognize, reward, and support good teaching within the University, the Board of Governors shall create annual system-wide teaching awards with monetary stipends which are designated the Board of Governors Awards for Excellence in Teaching.”
Professor Spremulli will be honored at the spring graduation ceremony, when a Board of Governors member will participate with Chancellor Thorp in presenting her an engraved bronze medallion and an award check.
"Linda clearly stands out as one of the finest teachers in our department's long history," said Chemistry Department Chair Matt Redinbo. "Former students still mention Linda specifically regarding courses they took twenty years ago. Talk about making an impact."
α-Oxyketones are important structural motifs commonly found in biologically active small molecules and natural products, and are versatile intermediates in organic synthesis. Typical approaches to α-oxyketone synthesis require pre-existing carbonyl groups that can be either oxidized or reduced. An attractive alternative strategy is the direct synthesis of α-oxyketones from alkenes via a multiple-electron oxidation, ketooxygenation. All prior ketooxygenations require the use of expensive and/or toxic transition-metal catalysts, such as Ru or Os, and are performed under harsh oxidizing conditions not readily amenable to complex molecular settings.
As reported in Chemical Science, the Alexanian Group has developed a metal-free ketooxygenation of alkenes using hydroxamic acids and O2. This process delivers α-oxyketones directly from simple alkenes with high levels of regio- and stereocontrol under mild conditions. This aerobic process is the fourth example published from the Alexanian Lab that highlights the unique reactivity of hydroxamic acids in intra- and intermolecular alkene addition reactions.
The pregnane X receptor (PXR), a member of the nuclear receptor superfamily, regulates the expression of drug-metabolizing enzymes in a ligand-dependent manner. The conventional view of nuclear receptor action is that ligand binding enhances the receptor's affinity for coactivator proteins, while decreasing its affinity for corepressors. To date, however, no known rigorous biophysical studies have been conducted to investigate the interaction among PXR, its coregulators, and ligands. In a collaborative work published in Biochemistry, researchers in the Thompson and Redinbo groups used steady-state total internal reflection fluorescence microscopy (TIRFM) and total internal reflection with fluorescence recovery after photobleaching to measure the thermodynamics and kinetics of the interaction between the PXR ligand binding domain and a peptide fragment of the steroid receptor coactivator-1 (SRC-1) in the presence and absence of the established PXR agonist, rifampicin.
Equilibrium dissociation and dissociation rate constants of 5 μM and 2 s-1, respectively, were obtained in the presence and absence of rifampicin, indicating that the ligand does not enhance the affinity of the PXR and SRC-1 fragments. Additionally, TIRFM was used to examine the interaction between PXR and a peptide fragment of the corepressor protein, the silencing mediator for retinoid and thyroid receptors (SMRT). An equilibrium dissociation constant of 70 μM was obtained for SMRT in the presence and absence of rifampicin. These results strongly suggest that the mechanism of ligand-dependent activation in PXR differs significantly from that seen in many other nuclear receptors.
Members of the Johnson Group describe in Organic Letters, how the three-component coupling of Mg acetylides, silyl glyoxylates, and nitroalkenes results in a highly diastereoselective Kuwajima–Reich/vinylogous Michael cascade that provides tetrasubstituted silyloxyallene products.
The regio- and diastereoselectivity were studied using DFT calculations. These silyloxyallenes were then converted to cyclopentenols and cyclopentitols via a unique Lewis acid assisted Henry cyclization. The alkene functionality present in the cyclopentanol products can be elaborated using diastereoselective ketohydroxylation reactions.
The 2012 edition of "Profiles in Team Science," published by the National Science Foundation, explores outcomes of team science that may not easily be covered within the constraints of the news media. The issue aims to bridge the news gap causing many members of the general public to be unaware of, or make connections between, research centers and the results they produce.
One of the articles highlights the work of the Center for Environmentally Responsible Solvents and Processes, CERSP, directed by Chancellor's Eminent Professor Joseph DeSimone. The center's initial goal was to establish the science enabling the replacement of aqueous and organic solvents in a large number of key processes in the manufacturing sector with liquid and supercritical CO2. Demonstrating the power of team science, CERSP's work led serendipitously to the PRINT technology. "It just shows the unbounded opportunities that happen when you get a bunch of good people together from different disciplines that are open-minded," says Professor DeSimone.
In Engines of Innovation, UNC Chapel Hill Chancellor Holden Thorp and Buck Goldstein, the University's "entrepreneur in residence," make the case for the pivotal role of research universities as agents of societal change. They argue that universities must use their vast intellectual and financial resources to confront global challenges such as climate change, extreme poverty, childhood diseases, and an impending worldwide shortage of clean water.
David Rohde, a a columnist for Reuters, two-time winner of the Pulitzer Prize, and a former reporter for The New York Times, discusses Engines of Innovation in a column in the journal Atlantic. Among examples of successful entrepreneuship started at universities, the article cites UNC chemistry professor Joe DeSimone as a best-case scenario. Last year, a private company DeSimone founded with the help of his university research received a $10 million investment from the Bill and Melinda Gates Foundation. The funding will help the company, Liquidia Technologies, develop new vaccines for malaria and other diseases.