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.
The Weeks Laboratory invents novel chemical microscopes for understanding the structure and functions of RNA and then applies these unique technologies to leading, and previously intractable, problems in biology. Current projects investigate the basic science of RNA chemistry; meld molecular chemistries with genome-scale readouts of RNA structure; focus on the genome structure and biology of human viruses, especially HIV; and create new therapeutics directed against viruses and human genetic disease. Most projects in the laboratory span fundamental chemistry or technology development and ultimately lead to practical applications in virology, next-generation structure analysis, or understanding biological processes in living cells. Collectively, this work has led to extensive recognition of student and postdoctoral colleagues in the laboratory.
Professor James Cahoon has had some very rewarding months. First, he was chosen as one of eighteen national recipients of a David and Lucile Packard Foundation Fellowship. He was elected as one of the nation's most innovative early-career scientists and engineers receiving a Packard Fellowships for Science and Engineering. Each Fellow will receive a grant of $875,000 over five years to pursue their research. "The Packard Fellowships are an investment in an elite group of scientists and engineers who have demonstrated vision for the future of their fields and for the betterment of our society," said Lynn Orr, Keleen and Carlton Beal Professor at Stanford University, and Chairman of the Packard Fellowships Advisory Panel.
As if that was not enough, he was then awarded a Sloan Research Fellowship by the Alfred P. Sloan Foundation. Given annually since 1955, the fellowships go to early career scientists and scholars whose achievements and potential identify them as rising stars, the next generation of scientific leaders. "These fellowship provide a well-deserved recognition of Jim's accomplishments and will help him continue his active research program," said Valerie Ashby, Professor and Chair of the Chemistry Department. "I have no doubt that his research efforts will be the source of major breakthroughs in the field of semiconductor nanomaterials and their exciting applications."
Just the other day, we also learned that James is one of 48 recipients of an Award from the Research Corporation for Science Advancement, RCSA, which supports "innovative research projects proposed by early career scientists at American colleges and universities." The awards cover a wide range of research in astronomy, chemistry, and physics.
“RCSA has always been about finding and supporting the next big scientific paradigm, the theory or discovery that will revolutionize and advance an entire field of study,” said RCSA President Robert N. Shelton. And noted all RCSA awards are subject to a critical peer-review process, which tends ensure that funding goes to the best and brightest among America's young academic scientists, the men and women who are likely to be leaders in their fields in the coming decades. Over the past century, 40 scientists receiving RCSA support have also earned the Nobel Prize, and many others have received significant honors in the physical sciences.
Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, researchers in the DeSimone Group, in a broadly collaborative work, have developed modalities for the localized iontophoretic delivery of cytotoxic agents. As described in Science Translational Medicine, these iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow.
Device therapy Compared to a control (left), mice treated with a chemotherapy drug using the device experienced significant growth reduction as confirmed by the lack of brown staining for a marker of tumor growth.
"Surgery to remove a tumor currently provides the best chance to cure pancreatic cancer," said DeSimone, Chancellor's Eminent Professor of Chemistry here at UNC, and William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at NC State University. "However, often a diagnosis comes too late for a patient to be eligible for surgery due to the tendency of the tumors to become intertwined with major organs and blood vessels." James Byrne, a member of the DeSimone Group, led the research by constructing the device and examining its ability to deliver chemotherapeutic drugs effectively to pancreatic cancer tumors, as well as two types of breast cancer tumors. Depending on the tumor type, the new device can be used either internally after a minimally invasive surgery to implant the device's electrodes directly on a tumor, or externally to deliver drugs through the skin. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.
Protein quinary interactions organize the cellular interior and its metabolism. Although the interactions stabilizing secondary, tertiary, and quaternary protein structure are well defined, details about the protein–matrix contacts that compose quinary structure remain elusive. This gap exists because proteins function in the crowded cellular environment, but are traditionally studied in simple buffered solutions.
Researchers in the Pielak Group use NMR-detected H/D exchange to quantify quinary interactions between the B1 domain of protein G and the cytosol of Escherichia coli. In their work, published in PNAS, the group demonstrates that a surface mutation in this protein is 10-fold more destabilizing in cells than in buffer, a surprising result that firmly establishes the significance of quinary interactions. Remarkably, the energy involved in these interactions can be as large as the energies that stabilize specific protein complexes. These results will drive the critical task of implementing quinary structure into models for understanding the proteome.
Congratulations to Professor Joseph DeSimone, winner of the 2014 Dickson Prize in Science, awarded annually to the person judged by Carnegie Mellon University to have made the most progress in the scientific field in the United States for the year in question. DeSimone was formally presented with the award during a February 16, 2015 ceremony where he delivered his Dickson Prize Lecture titled "Breakthroughs in Imprint Lithography and 3-D Additive Fabrication."
Light-activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light-sensitive prodrugs are typically converted to their active forms using short-wavelength irradiation, which displays poor tissue penetrance. Researchers in the David Lawrence Group report in Angewandte Chemie, International Edition, on erythrocyte-mediated assembly of long-wavelength-sensitive phototherapeutics.
The activating wavelength of the constructs is readily preassigned by using fluorophores with the desired excitation wavelength λex. Drug release from the erythrocyte carrier was confirmed by standard analytical tools and by the expected biological consequences of the liberated drugs in cell culture: methotrexate, binding to intracellular dihydrofolate reductase; colchicine, inhibition of microtubule polymerization; dexamethasone, induced nuclear migration of the glucocorticoid receptor.
In the perspective paper published in Computing in Science and Engineering’s special topic issue on Advances in Leadership Computing, researchers in the Kanai Group and his collaborators at University of Illinois at Urbana Champaign and Lawrence Livermore National Laboratory describe the state-of-the-art computational method for simulating quantum dynamics of electrons in complex materials using supercomputers.
They discuss a new first-principles computational method for simulating quantum dynamics of electrons in complex materials by propagating time-dependent wavefunctions. The method is designed to take advantage of a large number of processing cores in today’s supercomputers by utilizing multiple levels of different parallelization schemes. They demonstrate a strong scaling of the computational method over 1 million processing cores on an IBM supercomputer. As an example of how new material properties can be investigated using this state-of-the-art method, non-equilibrium energy transfer rate from a fast proton to the electronic excitation in bulk gold was calculated and compared to available experimental data. Importantly, the computer simulation provides detail information on how the electronic excitation is induced by the fast proton. This new first-principles quantum dynamics method enables theoretical investigations into various non-equilibrium phenomena of electrons in large complex systems.
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."