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 Gagné Lab is interested in the development of new synthetic methods for complex bond constructions. To mimic sterol biosynthesis, we have developed several "carbophilic" late metal catalysts (Pd, Pt, and Au) for alkene and allene activation, while in other projects we seek new catalysts for glycosidic C-O bond activation. The goal in this latter project is to use polysaccharides as renewable feedstocks for complex molecule synthesis. A third major thrust is in dynamic combinatorial chemistry (DCC), a dynamic templating strategy that selects for new receptors under competitive binding conditions. This strategy is additionally being used for new catalyst discovery.
Nancy Allbritton, the Paul Debreczeny Distinguished Professor of Chemistry and Chair of the UNC/NC State joint Department of Biomedical Engineering, has been named a fellow of the National Academy of Inventors. The honor is awarded to academic inventors who have a prolific spirit of innovation in creating outstanding inventions that have made a tangible impact on quality of life, economic development and the welfare of society. Allbritton was also recently elected a fellow of the American Association for the Advancement of Science, AAAS.
The innovators elected as NAI fellows are named inventors on U.S. patents and were nominated by their peers for outstanding contributions to innovation in areas such as patents and licensing, innovative discovery and technology, significant impact on society, and support and enhancement of innovation.
We congratulate Assistant Professor James Cahoon as being one of eighteen national recipients of a David and Lucile Packard Foundation Fellowship. James was elected as one of the nation's most innovative early-career scientists and engineers receiving a 2014 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. "Through the Fellowships program, we are able to provide these talented individuals with the tools and resources they need to take risks, explore new frontiers and follow uncharted paths."
Francis Preston Venable Professor of Chemistry, Joseph Templeton, is the recipient of this year's Thomas Jefferson award, which was presented to him by Chancellor Folt at a recent Faculty Council meeting. "I would just like to add from my own chance to work so closely with Professor Templeton the last year how deserving and wonderful this award is," said Chancellor Folt.
The Thomas Jefferson Award was established in 1961 by the Robert Earll McConnell Foundation. It is presented annually to "that member of the academic community who through personal influence and performance of duty in teaching, writing, and scholarship has best exemplified the ideals and objectives of Thomas Jefferson." This award is, according to Department Chair, Professor Valerie Ashby, "a well-deserved honor for Professor Templeton that recognizes the many forms of his contributions to the university throughout his career."
A new small molecule receptor, A2N, has been identified that binds specifically to trimethyllysine, Kme3, with sub-micromolar affinity. This receptor, as published in Organic & Biomolecular Chemistry was discovered by Nicholas Pinkin and Marcey Waters in the Waters Group, through the iterative redesign of a monomer known to incorporate through dynamic combinatorial chemistry, DCC, into a previously reported receptor for Kme3, A2B. In place of monomer B, the newly designed monomer N introduces an additional cation–Π interaction into the binding pocket, resulting in more favorable binding to Kme3 amounting to a ten-fold improvement in affinity and a five-fold improvement in selectivity over Kme2.
This receptor exhibits the tightest affinity and greatest selectivity for Kme3-containing peptides reported to date. Comparative studies of A2B and A2N provide mechanistic insight into the driving force for both the higher affinity and higher selectivity of A2N, indicating that the binding of Kme3 to A2N is both enthalpically and entropically more favorable. This work demonstrates the ability of iterative redesign coupled with DCC to develop novel selective receptors with the necessary affinity and selectivity required for biological applications.
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.
Genetically encoded, light-activatable proteins provide the means to probe biochemical pathways at specific subcellular locations with exquisite temporal control. However, engineering these systems in order to provide a dramatic jump in localized activity, while retaining a low dark-state background remains a significant challenge.
When placed within the framework of a genetically encodable, light-activatable heterodimerizer system, the actin-remodelling protein cofilin induces dramatic changes in the F-actin network and consequent cell motility upon illumination. In an article published in Angewandte Chemie, International Edition, researchers in the David Lawrence Group, demonstrate that the use of a partially impaired mutant of cofilin is critical for maintaining low background activity in the dark. They also show that light-directed recruitment of the reduced activity cofilin mutants to the cytoskeleton is sufficient to induce F-actin remodeling, formation of filopodia, and directed cell motility.
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."