David J. Eide

Professor of Nutritional Sciences
B.S. 1981, University of Minnesota
Ph.D. 1987, University of Wisconsin

Emphasis Group(s):
Biochemical and Molecular Nutrition

Research Interests:
Nutritional genomics and molecular responses to changes in nutrient status.

Research Summary: 
Our research is focused on the mechanism of transition metal uptake in eukaryotic cells and how this process is regulated in response to changes in the availability of metal ions in the diet or the environment. We are using the yeast Saccharomyces cerevisiae as a model system for understanding these processes in mammals and plants.  Questions our research is currently addressing include: 1) What transport proteins are responsible for the uptake and intracellular distribution of metals in yeast and how do they work?  2) How is the activity of these transporters regulated in response to metal-deprivation and excess? 3) What other genes are required for adaptation to low zinc conditions? 4) Can we use the reagents and insights generated in our studies  of yeast to better understand metal ion homeostasis in higher eukaryotes?  The figure shows one of the zinc-sensing domains of the yeast Zap1 transcription factor.  This small domain (~60 residues in length) is the portion of the 880 amino acid Zap1 protein that activates transcription of over 50 genes in the yeast genome.  When zinc is abundant, the metal binds to this domain to form two zinc fingers (ZF1 and ZF2) of the C2H2 type first identified in transcription factor TFIIIA.  This results in the folding of the domain into the repressed conformation shown in the figure that is unable to activate target gene transcription.  Thus, evolution has co-opted a zinc-binding structural domain, the zinc finger, to use as a sensor of zinc status in the cell.

Representative Publications:

- Ellis, C., MacDiarmid, C., and Eide, D. Heteromeric protein complexes mediate zinc transport into the secretory pathway of eukaryotic cells. J. Biol. Chem. 280:28811-28818 (2005).

- Qiao, W., Mooney, M., Bird, A., Winge, D., and Eide, D.  Zinc binding to a regulatory zinc-sensing domain monitored in vivo using fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. USA, 103:8674-8679 (2006).

- Wu, C., Bird, A., Winge, D. and Eide, D. Regulation of the yeast Tsa1 peroxiredoxin by Zap1 is an adaptive response to the oxidative stress of zinc deficiency. J. Biol. Chem. 282:2184-2195 (2007).

-  Simm, C., Lahner, B., Salt, D., LeFurgey, A., Ingram, P., Yandell, B., and Eide, D.  The yeast vacuole in zinc storage and intracellular zinc distribution.  Euk. Cell, 6:1166-1177 (2007).