Ph.D. Cornell University
NMR is a well-suited technique to investigate structural and dynamic changes of proteins in solution. As the home of the School of Biological Sciences (SBS) NMR Facility, we are using NMR and other biophysical and molecular biology approaches to explore several aspects of zinc finger transcription factor biology. A major focus of the lab is to characterize the molecular mechanisms that control divalent zinc [Zn(II)] homeostasis in yeast and mammalian cells. All known organisms require Zn(II), and yet this essential nutrient is toxic if accumulated to excess. Zn(II) homeostasis in mammalian and yeast cells is regulated at least in part at the level of coordination chemistry by two zinc finger proteins, Zap1 (yeast) and MTF-1 (mammalian). MTF-1 and Zap1 are transcription factors that control the expression of proteins to transport Zn(II) in or out of the cellular compartments [Zn(II) transport proteins] or to sequester Zn(II) through high-affinity metal-ligand coordination (metallothioneins). Studies on MTF-1 involve a close collaboration with Dr. Glen Andrews at the neighboring University of Kansas Medical Center, Department of Molecular Biology and Biochemistry. A new area of focus in the lab centers on understanding the molecular mechanisms whereby a special group of zinc finger-containing Zic family transcription factors regulate key processes that are essential for human brain development. These studies are ongoing in close collaboration with Dr. Gerald Wyckoff in the SBS. In two additional collaborative projects, we are exploring the molecular mechanisms of targeted elements of bacterial pathogenesis. We are currently collaborating with Dr. Lawrence Dreyfus, Dean of the UMKC, SBS to explore the structure/function relationships that underlie the cytotoxic effects of the cytolethal distending toxin. In a second collaboration with Dr. Brian Geisbrecht (SBS), we are investigating structural and dynamic aspects of antigen/receptor interactions. We acknowledge current and prior funding for these projects from The National Institutes of Health and the University of Missouri Research Board.