Eukaryotic cells are composed of many different compartments, such as mitochondria and nuclei. Although each of these compartments exhibits a distinct set of metabolic processes, they must all communicate with each other for the cell to function properly. Understanding how these processes are organized and controlled represents the next frontier in the study of metabolism. We have focused our efforts on folate-mediated one-carbon metabolism. This set of pathways is found in all cells and organisms, is central to fundamental processes such as nucleic acid and protein synthesis, and occurs in multiple compartments. We utilize a wide variety of biochemical and molecular genetic techniques, as well as nuclear magnetic resonance, to study the organization of these pathways in both mammalian and yeast systems. The use of noninvasive techniques such as NMR has revealed metabolic relationships and interactions that were overlooked in traditional in vitro systems.

The molecular organization of a metabolic pathway is ultimately dependent on the unique three-dimensional structures of the individual enzyme components. Thus, we have several protein structure projects ongoing in the laboratory. Techniques include kinetic analysis, site-directed mutagenesis, and X-ray crystallography (in collaboration with Dr. Robertus). Our goal is to understand how these enzymes function and interact with one another in the cell.