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: 
In our research, we ask a basic question in biology, i.e. how do cells respond to an ever-changing environment of nutrient availability? This is a fundamental issue for all organisms including free-living and pathogenic microbes, as well as multicellular organisms such as plants and mammals.Our studies are focused on zinc, an essential metal nutrient, and the yeast Saccharomyces cerevisiae. This simple eukaryote has proven to be a great model for the study of many important cellular processes including the responses of cells to conditions of nutrient stress. The success of yeast as an experimental model stems from our ability to manipulate this organism using genetics and molecular biology.

In S. cerevisiae, the Zap1 transcription factor is the key player in the response to zinc deficiency. This metal-responsive regulatory protein controls the expression of many genes in yeast. For most of its target genes, Zap1 acts as a transcriptional activator and increases expression when zinc levels are low. In a few other cases, Zap1 acts as a transcriptional repressor. Using transcriptome profiling with DNA microarrays and other approaches, we have discovered that Zap1 regulates many genes in the yeast genome. These studies indicate that more than 80 genes in yeast are direct targets of Zap1 activation. In addition, over 30 genes are repressed in a Zap1-dependent manner indicating that additional modes of regulation exist.

This collection of Zap1-regulated genes is providing exciting new insights into how cells respond to nutrient stress. These strategies of stress response include up-regulation of plasma membrane zinc uptake transporters and transporters responsible for mobilizing intracellular stores of zinc. In addition, transporters responsible for moving zinc into organelles such as the endoplasmic reticulum are also induced. Collectively, we refer to these as “homeostatic” responses because they serve to maintain zinc levels within the cell. We have also discovered a number of other responses that play an “adaptive” role. These adaptive responses aid cell growth under conditions of zinc deficiency and include remodeling of phospholipid synthesis, oxidative stress tolerance, and sulfate assimilation. All together, we have characterized the role of about 25 of the more than 100 Zap1 target genes. Much of our future work will be directed toward understanding the role of the other ~80 Zap1 targets. The analysis of these genes will provide great insight into how cells of all organisms deal with the stress of nutrient deficiency.

Representative Publications:

Eide, D.J. Homeostatic and adaptive responses to zinc deficiency in Saccharomyces cerevisiae. J. Biol. Chem. 284: 18565-18569 (2009)

Qiao, W., Ellis, C., Steffen, J., Wu, C., and Eide, D. Zinc status and vacuolar zinc transporters control alkaline phosphatase accumulation and activity in Saccharomyces cerevisiae. Mol. Microbiol. 72:320-34 (2009).

Wu, C., Bird, A., Chung, L., Newton, M., Winge, D., and Eide, D. Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae. BMC Genomics, 9:370 (2008).

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).

Mao, X., Kim, B., Wang, F., Eide, D., and Petris, M. A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. J. Biol. Chem. 282:6992-7000 (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. Eukaryotic Cell, 6:1166-77 (2007).

Bird, A., Gordon, M., Eide, D., and Winge, D. Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts. EMBO J. 25:5726-5734 (2006).