Research in the Wightman Group is directed at the development of microsensors and their use to measure chemical events in microenvironments. We have developed ultramicroelectrodes that are robust chemical sensors, which can resolve chemical events with micron or submicron spatial resolution. In addition, these probes can be used for measurements on the nanosecond time scale and in environments in which electrochemical measurements are normally impossible.
The Lawrence Group works at the interface between organic synthesis and cell biology. In fact, half the group resides in Chemistry's Kenan Labs and the other half can be found in the newly opened multidisciplinary Genetic Medicine Building in the medical school complex. The lab focuses on the design, synthesis, characterization, and application of probes of intracellular chemistry. Research interests include new diagnostic strategies for cancer, sensors of signaling pathways, mitochondrial proteomics, the molecular basis of memory and learning, and the control of gene expression in living animals.
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.
Protein arginine methyltransferase 10 (PRMT10) is a type I arginine methyltransferase that is essential for regulating flowering time in Arabidopsis thaliana. Scientists in the Redinbo Group present in the Journal of Molecular Biology, a 2.6 Å resolution crystal structure of A. thaliana PRMT 10 (AtPRMT10) in complex with a reaction product, S-adenosylhomocysteine. The structure reveals a dimerization arm that is 12–20 residues longer than PRMT structures elucidated previously; as a result, the essential AtPRMT10 dimer exhibits a large central cavity and a distinctly accessible active site.
The researchers employed molecular dynamics to examine how dimerization facilitates AtPRMT10 motions necessary for activity, and they show that these motions are conserved in other PRMT enzymes. Finally, functional data reveal that the 10 N-terminal residues of AtPRMT10 influence substrate specificity, and that enzyme activity is dependent on substrate protein sequences distal from the methylation site. Taken together, these data provide insights into the molecular mechanism of AtPRMT10, as well as other members of the PRMT family of enzymes. They highlight differences between AtPRMT10 and other PRMTs but also indicate that motions are a conserved element of PRMT function.
Polymer solar cells have some noteworthy advantages over mainstream inorganic-based solar cells, such as significantly reduced material/fabrication costs, flexible substrates, and low weight of finished solar cells. Thus polymer-based solar cells have become a very intensely researched field, interfacing chemistry, physics, and engineering. Rapid progress has been made with, for example, reports of power-conversion efficiency as high as 10%.
The central question — how to rationally design polymers to reach higher efficiency — has remained at the top of research priorities. As leaders in the design and synthesis of conjugated polymers for solar cells, researchers in the You Group attempt to answer this core question in a Perspective published as a cover article in the journal Macromolecules. From their unique vantage point, Huaxing Zhou, Liqiang Yang, and Wei You comprehensively review the progress in the polymer materials design for solar cells in the past decade and a half. Additionally, they offer inspiring recommendations in the section of "Outlook and Challenges," hoping to stimulate the field to come up with new ideas to push the efficiency even higher, to 15% and beyond.
In the Game of Life, when the opponents in your tournament bracket include the greatest problems of our time, it takes strategy and teamwork to seek solutions. And while UNC and Duke are rivals on the basketball court, the two schools' faculty, staff and students often join forces to take on pressing global, national and local issues and challenges. One example is the collaborative research on new alternative energy, performed by the UNC/Duke Energy Frontier Research Center. This Tar Heel/Blue Devil "Dream Team" has great offense and defense, a strong roster and plays well both at home and on the road.
Bottom line: Even if they do not take the champion's crown in this year's Game of Life Tournament, the Tar Heel/Blue Devil "Dream Team" is a strong contender and will have a major influence on the outcome.
However, this formidable alliance is sometimes put on hold: come tip off at the big UNC vs. Duke basketball game tonight, we are pretty sure which shades of blue our respective students, faculty and staff will be wearing.
Histone lysine methylation is a critical marker for controlling gene expression. The position and extent of methylation controls the binding of effector proteins that determine whether the associated DNA is expressed or not. Dysregulation of histone protein methylation has been associated with a number of types of cancer, and development of inhibitors for the effector proteins is becoming an active area of research.
Mutation studies performed by scientists in the Waters Group, published in ChemBioChem, provide insight into the role of electrostatic interactions and hydrogen bonding in the differentiation of methylation states and have implications regarding the evolutionary pressure for selectivity in this protein–protein interaction. Moreover, the information from this study may help guide inhibitor development for this class of proteins.
RNA is the central conduit for information transfer in our biosphere. This role depends critically on an ability to encode information at two levels: both in its linear sequence and in the complex structures RNA forms by folding back on itself.
A review by Professor Kevin Weeks and American Cancer Society Fellow David Mauger, featured on the cover of Accounts of Chemical Research, discusses rapidly evolving work in the Weeks laboratory focused on creating facile, generic, quantitative, accurate, and highly informative approaches for understanding RNA structure in biologically important environments. These chemistry-based technologies, collectively called RNA SHAPE, are now employed extensively worldwide.