Norman J. Dovichi
Grace-Rupley Professor of ChemistryDepartment of Chemistry and Biochemistry
University of Notre Dame
Notre Dame, IN
The Dovichi group is a bio-analytical research laboratory, specializing in instrument development. The group’s goal is to study protein expression and metabolism pathways in single cells, which are necessary to understand health and disease. Various areas of research within the group include separations by capillary electrophoresis-laser induced fluorescence (CE-LIF) and capillary electrophoresis-mass spectrometry (CE-MS), the development of mass spectrometry-based proteomic analysis, photothermal lens microscopy, and other projects that the group members find interesting. Now that the [human and Xenopus] genomes are sequenced, interest is focused on the study of the proteome, which is the protein content of an organism, tissue, or cell. The Dovichi group is developing tools to study the proteome with two-dimensional capillary electrophoresis, coupled to either laser-induced fluorescence or mass spectrometry for detection. The group's long-term goal is to study protein expression in single cells and to determine how protein expression changes across a cellular population during cancer progression and during the development of an embryo. In the shorter term, we are developing tools to characterize post-translational modifications of proteins and to speed digestion and analysis of proteins. Proteomics provides a parts list for a cell; it does not necessarily describe how those parts function. Ultimately, the characterization of a cells metabolism, which describes the production and consumption of small molecules, is necessary to understand health and disease. The Dovichi group also is studying metabolic pathways in single cells. In general, a fluorescent substrate is synthesized. Any enzymatic transformation of the substrate can be monitored with exquisite sensitivity as long as the fluorescent label is preserved. We are collaborating with Ole Hindsgaul and Monica Palcic of the Carlsberg Institute and Ron Schnaar at Johns Hopkins University to characterize sphingolipid metabolism in single cells. These glycolipids make up a very large fraction of neuronal membrane, and defects in their metabolism leads to devastating genetic diseases.