Biological assays have dramatically improved in recent years due to the increasing use of living cells as "test tubes" for research studies. These cell-based assays have demanded that new technologies be developed for the life sciences in order to fully exploit the potential of designer drugs, stem cell engineering, and genetic medicine. The Allbritton Group is at the forefront of this technology development for biomedical and pharmaceutical research.
Micropallet Technology
In the area of cloning for cancer and stem cell studies, the Allbritton group demonstrated a novel and effective approach for the isolation of specific, single cells from a population of cells. Using principles borrowed from the electronics industry, microengineered arrays of extremely small structures (30 – 50 microns) termed micropallets are fabricated on the surface of a microscope slide. A laser is used to detach an individual micropallet and its attached cell from the slide whereupon it is collected. This strategy has been demonstrated for single-cell isolation with unprecedented survival and colony forming ability of single cells (>85%), thus dramatically improving the cloning process. This tool is now under development in an NIH-funded project with Mike Ramsey in the Department of Chemistry and colleagues in the Lineberger Cancer Center's Animal Models Facility to improve the process for creating genetically modified mice for medical research.
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.
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.
Francis Preston Venable Professor of Chemistry Joseph L. Templeton has been awarded the General Alumni Association's Faculty Service Award. The award was established in 1990 and honors faculty members who have performed outstanding service for the University or the association. Templeton was the faculty representative on the GAA board for 2009-10.
As Templeton — who served as chair of the chemistry department from 1990 to 1995 — has continued to teach a full course load, mentor graduate students, apply for grants and run his own research projects, he also has taken on several high-profile administrative assignments. Among other duties, he served as chair of the Faculty Council from 2006 to 2009, served as chair of the Summer Reading Program Book Selection Committee, on the Chancellor’s Advisory Committee, and the Faculty Executive Committee.
Mammalian mitochondrial translational initiation factor 3 (IF3mt) binds to the small subunit of the ribosome displacing the large subunit during the initiation of protein biosynthesis. About half of the proteins in mitochondrial ribosomes have homologs in bacteria while the remainder are unique to the mitochondrion. To obtain information on the ribosomal proteins located near the IF3mt binding site, researchers in the Spremulli Group, in collaboration with colleagues at the Department of Biochemistry and Molecular Biology, Pennsylvania State University, performed cross-linking studies, followed by identification of the cross-linked proteins by mass spectrometry. Their results are published in Biochimica et Biophysica ACTA (BBA) - Proteins & Proteomics.
IF3mt cross-links to mammalian mitochondrial homologs of the bacterial ribosomal proteins S5, S9, S10, and S18-2 and to unique mitochondrial ribosomal proteins MRPS29, MRPS32, MRPS36 and PTCD3 (Pet309) which has now been identified as a small subunit ribosomal protein. IF3mt has extensions on both the N- and C-termini compared to the bacterial factors. Cross-linking of a truncated derivative lacking these extensions gives the same hits as the full length IF3mt except that no cross-links were observed to MRPS36. IF3 consists of two domains separated by a flexible linker. Cross-linking of the isolated N- and C-domains was observed to a range of ribosomal proteins particularly with the C-domain carrying the linker which showed significant cross-linking to several ribosomal proteins not found in prokaryotes.
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.
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.
Nanoscale coordination polymers (NCPs) have been demonstrated as an interesting platform for the delivery of methotrexate (MTX), an antifolate cancer drug, as they possess many potential advantages over small-molecule chemotherapeutics such as high payloads, lower systemic toxicity, tunability, and enhanced tumor uptake. NCPs also overcome the limitations of existing nanoparticle formulations that have very low drug loadings.
Researchers in the Lin Group, published in Chemical Science, report the incorporation of MTX as a building block in an NCP formulation with exceptionally high drug loadings (up to 79.1 wt%) and the selective delivery of the NCP to cancer cells. Encapsulation of the NCP in a functionalized lipid bilayer allows for targeted delivery and controlled release to cancer cells. A phosphor can be doped into the NCPs for monitoring particle uptake by optical imaging. The lipid-coated and anisamide-targeted NCPs have superior in vitro efficacy against acute lymphoblastic leukemia cells when compared to the free drug.