Department of Chemistry

Biochemistry & Chemical Biology

Research ImageGraduate students in biochemistry and chemical biology meld molecular and structural biology with physical, organic and analytical chemistry to understand the molecular basis of biological processes and of human disease. Research in the Biochemistry and Chemical Biology Division focuses on the structure and function of proteins, membranes, DNA, RNA, large macromolecular complexes and viruses, natural product biogenesis, synthetic biology, and genomics.

Students are a constant source of new hypotheses for mechanisms underlying cellular machines like the ribosome and spliceosome, and for the protein and RNA folding problems. Students tackle these problems using biochemical methods, chemical biosensor technologies, protein and nucleic acid crystallography, in vitro and in vivo evolution, multi-dimensional NMR spectroscopy, surface chemistry, atomic force microscopy, fluorescence spectroscopy, and high-resolution mass spectrometry.

Doctoral students in Biochemistry and Chemical Biology leave the Department broadly trained for leadership roles in academia and industry.

 

 

 

Potential Pancreatic Cancer Treatment

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.

Research Image

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.

 

Quinary Structure Modulates Protein Stability

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.

Research Image

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.

 

Representative Publications

In-Cell SHAPE Reveals that Free 30S Ribosome Subunits are in the Inactive State. Jennifer L. McGinnis, Qi Liu, Christopher A. Lavender, Aishwarya Devaraj, Sean P. McClory, Kurt Fredrick, and Kevin M. Weeks. PNAS, vol. 112 no. 8, 2425–2430, doi: 10.1073/pnas.1411514112.

Hydrogen Exchange of Disordered Proteins in Escherichia coli. Austin E. Smith, Larry Z. Zhou and Gary J. Pielak. Protein Science, Volume 24, Issue 5, pages 706–713, May 2015.

Hydrogen Exchange of Disordered Proteins in Escherichia coli. Austin E. Smith, Larry Z. Zhou and Gary J. Pielak. Protein Science, Volume 24, Issue 5, pages 706–713, May 2015.

Enzymatic Basis of "Hybridity" in Thiomarinol Biosynthesis. Zachary D. Dunn, Walter J. Wever, Dr. Nicoleta J. Economou, Prof. Albert A. Bowers andProf. Bo Li. Angewandte Chemie International Edition, Volume 54, Issue 17, pages 5137–5141, April 20, 2015.

Enzymatic Basis of "Hybridity" in Thiomarinol Biosynthesis. Zachary D. Dunn, Walter J. Wever, Dr. Nicoleta J. Economou, Prof. Albert A. Bowers and Prof. Bo Li. Angewandte Chemie International Edition, Volume 54, Issue 17, pages 5137–5141, April 20, 2015.

Multicolor Monitoring of the Proteasome's Catalytic Signature. Melanie A. Priestman, Qunzhao Wang, Finith E. Jernigan, Ruma Chowdhury, Marion Schmidt, and David S. Lawrence. ACS Chem. Biol., 2015, 10 (2), pp 433–440.

Local Iontophoretic Administration of Cytotoxic Therapies to Solid Tumors. James D. Byrne, Mohammad N. R. Jajja, Adrian T. O’Neill, Lissett R. Bickford, Amanda W. Keeler, Nabeel Hyder, Kyle Wagner, Allison Deal, Ryan E. Little, Richard A. Moffitt, Colleen Stack, Meredith Nelson, Christopher R. Brooks, William Lee, J. Chris Luft, Mary E. Napier, David Darr, Carey K. Anders, Richard Stack, Joel E. Tepper, Andrew Z. Wang, William C. Zamboni, Jen Jen Yeh, and Joseph M. DeSimone. Sci Transl Med 4 February 2015: Vol. 7, Issue 273, p. 273ra14.

Quinary Structure Modulates Protein Stability in Cells. William B. Monteith, Rachel D. Cohen, Austin E. Smith, Emilio Guzman-Cisneros, and Gary J. Pielak. PNAS, Early Edition, doi 10.1073 pnas.1417415112 .

Cell-Mediated Assembly of Phototherapeutics. Weston J. Smith, Nathan P. Oien, Robert M. Hughes, Christina M. Marvin, Zachary L. Rodgers, Junghyun Lee and David S. Lawrence. Angewandte Chemie International Edition, Volume 53, Issue 41, pages 10945-10948, October 6, 2014.

Optogenetic Engineering: Light-Directed Cell Motility. Robert M. Hughes and David S. Lawrence. Angewandte Chemie International Edition, Volume 53, Issue 41, pages 10904-10907, October 6, 2014.