The Redinbo Laboratory uses the tools of structural, molecular and chemical biology to examine a range of dynamic cellular processes central to human health. Current projects include the discovery of new antimicrobials targeted to drug-resistant bacteria, the design of novel proteins engineered to detect and eliminate toxic chemicals, and the development of small-molecule to cell-based methods to improve anticancer chemotherapeutics. In addition, we continue to focus on determining the crystal structures of macromolecular complexes, including those involving human nuclear receptors central to transcriptional regulation, bacterial proteins involved in DNA manipulation and human cell contact, and enzymes central to key cellular processes.
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.
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 â€“ 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.
On October 22nd through 24th, the Chemistry Department will host a symposium to commemorate the 10th anniversary of the death of Roger Miller, Professor of Chemistry at UNC from 1984 – 2005. Invited speakers include Professor Michael Duncan, University of Georgia, David Nesbitt, University of Colorado, former Miller students, as well as UNC faculty and students.
Sphingosine-1-phosphate, S1P, a lipid second messenger formed upon phosphorylation of sphingosine by sphingosine kinase ,SK, plays a crucial role in natural killer, NK, cell proliferation, migration, and cytotoxicity. Dysregulation of the S1P pathway has been linked to a number of immune system disorders and therapeutic manipulation of the pathway has been proposed as a method of disease intervention.
However, peripheral blood NK cells consist of a highly diverse population with distinct phenotypes and functions and it is unknown whether the S1P pathway is similarly diverse across peripheral blood NK cells. In a collaborative work, published as a cover article in Integrative Biology, researchers in the Allbritton Group, measured the phosphorylation of sphingosine–fluorescein, SF, and subsequent metabolism of S1P fluorescein, S1PF, to form hexadecanoic acid fluorescein, HAF, in 111 single NK cells obtained from the peripheral blood of four healthy human subjects. Substantial heterogeneity in S1P production and metabolism across cells within and between subjects was readily apparent. NK-cell subpopulations may exist with respect to SK activity and individual humans may possess distinct phenotypes. A deeper understanding of lipid signaling at the single-cell level will be critical to understand NK cell biology and disease.
It has been known for decades that the ribosome, the cellular complex that synthesizes proteins, interconverts between "active" and "inactive" conformations. However, the physiological relevance of this widely observed switch remained unclear and unknown.
Jennifer McGinnis, in the Weeks Lab, led a study, published in PNAS, in which newly developed in-cell SHAPE technologies were used to probe the structure of the ribosome in healthy living cells. In cells, one class of ribosome subunits exists predominantly in the classic "inactive" conformation and disrupting the ability to interconvert between active and inactive conformations compromises protein synthesis. In-cell RNA structure probing thus resolved this 40 year old challenge to reveal that the inactive state regulates ribosome function as a conformational switch.
Undergraduate placement exam will be given on
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A truly disordered protein lacks a stable fold and its backbone amide protons exchange with solvent at rates predicted from studies of unstructured peptides. In a paper published in Protein Science, Austin Smith, a graduate student in the Pielak Group have measured the exchange rates of two model disordered proteins, FlgM and α-synuclein, in buffer and in Escherichia coli using the NMR experiment, SOLEXSY.
The rates are similar in buffer and cells and are close to the rates predicted from data on small, unstructured peptides. This result indicates that true disorder can persist inside the crowded cellular interior and that weak interactions between proteins and macromolecules in cells do not necessarily affect intrinsic rates of exchange. Parenthetically, the research Austin did for this paper earned him the Best Poster Award at the Protein Society's annual conference last year.
Copper metal is in theory a viable oxidative electrocatalyst based on surface oxidation to CuIII and/or CuIV, but its use in water oxidation has been impeded by anodic corrosion. Researchers from the Meyer Group, published in Angewandte Chemie, present the in situ formation of an efficient interfacial oxygen-evolving Cu catalyst from CuII in concentrated carbonate solutions.
The catalyst necessitates use of dissolved CuII and accesses the higher oxidation states prior to decompostion to form an active surface film, which is limited by solution conditions. This observation and restriction led to the exploration of ways to use surface-protected Cu metal as a robust electrocatalyst for water oxidation. Formation of a compact film of CuO on Cu surface prevents anodic corrosion and results in sustained catalytic water oxidation. The Cu/CuO surface stabilization was also applied to Cu nanowire films, which are transparent and flexible electrocatalysts for water oxidation and are an attractive alternative to ITO-supported catalysts for photoelectrochemical applications.
At the Department of Chemistry, we feel strongly that diversity is crucial to our pursuit of academic excellence, and we are deeply committed to creating a diverse and inclusive community. We support UNC's policy, which states that "the University of North Carolina at Chapel Hill is committed to equality of opportunity and pledges that it will not practice or permit discrimination in employment on the basis of race, color, gender, national origin, age, religion, creed, disability, veteran's status, sexual orientation, gender identity or gender expression."