Research in the Bird lab focuses on metal ion homeostasis in eukaryotic cells. Metal ions including zinc, copper, iron, and manganese, are required for the function of approximately one third of all proteins and one half of all enzymes. Although we know much about the function of a given metal within a protein, we know relatively little about the processes by which cells maintain sufficient levels of ‘available’ metal ions for incorporation into newly synthesized proteins. As too much or too little of any metal is detrimental to human health, the long-term goals of our research are to determine how cells maintain optimal levels of labile metal ions for incorporation into folding polypeptides, and how proteins obtain their correct metal cofactors in vivo. To gain insight into these universal processes we use the fission yeast Schizosaccharomyces pombe as a model system to study how cells maintain optimal levels of zinc within the cytosol and organelles. We also investigate how metallo-enzymes within the secretory pathway preferentially bind to correct metal cofactors. As the regulation of metal ions is universal to all cells, our research will provide insight into how metal ion homeostasis and metal ion selectivity is regulated in higher eukaryotes.
Choi S, Hu Y-M, Corkins ME, Palmer AE, and Bird AJ (2018) Zinc transporters belonging to the Cation Diffusion Facilitator (CDF) family have complementary roles in transporting zinc out of the cytosol. PLOS Genetics (in press)
Bird AJ and Labbé S (2017) The Zap1 transcriptional activator negatively regulates translation of the RTC4 mRNA through the use of alternative 5' transcript leaders. Mol. Microbiol 106:673-677.
Corkins ME, Wilson S, Cocuron JC, Alonso AP, and Bird AJ (2017) The gluconate shunt is an alternative route for directing glucose into the pentose phosphate pathway in fission yeast. J Biol Chem 292:13823-13832
Wilson S and Bird AJ (2016) Zinc sensing and regulation in yeast model systems. Arch Biochem and Biophys. 611:30-36
Bird AJ (2015) Cellular sensing and transport of metal ions: implications in micronutrient homeostasis. J. Nutr. Biochem. 26:1103-1115
Ehrensberger KM, Corkins ME, Choi S, and Bird AJ (2014) The Double Zinc Finger Domain and Adjacent Accessory Domain from the Transcription Factor Loss of Zinc Sensing 1 (Loz1) Are Necessary for DNA Binding and Zinc Sensing". J Biol Chem. 289:18087-18096
Choi S, and Bird AJ (2014) Zinc’ing sensibly: controlling zinc homeostasis at the transcriptional level. Metallomics 6:1198-1215
Corkins ME, May M, Ehrensberger KM, Hu YM, Liu YH, Bloor SD, Jenkins B, Runge KW, Bird AJ (2013) Zinc finger protein Loz1 is required for zinc-responsive regulation of gene expression in fission yeast. Proc Natl Acad Sci USA 103:8674-79.
Ehrensberger KE, Mason C, Corkins, ME, Anderson C, Dutrow N, Cairns B, Dalley B, Milash B, and Bird AJ (2013) Zinc-dependent regulation of the adh1 antisense transcript in fission yeast. J Biol Chem. 288:759-769
Ehrensberger KE and Bird AJ (2011) Hammering out details: Regulating metal levels in eukaryotes. TIBS 36:524-31
Frey AG, Bird AJ, Blankman E, Evans-Galea M, Winge DR, and Eide DJ (2011) Zinc-regulated DNA Binding of the yeast Zap1 zinc-responsive activator. PLOS One 6:e22535
Wu CY, Roje S, Sandoval FJ, Bird AJ, Winge DR, and Eide DJ (2009) Repression of sulfate zinc assimilation is an adaptive response of yeast to the oxidative stress of deficiency. J Biol Chem 284:27544-56
Wu CY, Bird AJ, Chung LM, Newton MA, Winge DR, and Eide DJ (2008) Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae. BMC Genomics 9:370-387
Khalimonchuk O, Bird AJ, and Winge DR (2007) Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase. J Biol Chem 282:17442-9
Bird AJ (2007) Metallosensors, the ups and downs of gene regulation. Adv Microb Physiol 53:232-57
Bird AJ, Gordon M, Eide DJ, and Winge DR (2006) Repression of ADH1 and ADH3 gene expression during zinc deficiency by Zap1-induced intergenic RNA transcripts. EMBO J 25:5726-34
Wu CY, Bird AJ, Winge DR, and Eide DJ (2006) Regulation of the yeast Tsa1 peroxiredoxin by Zap1 is an adaptive response to the oxidative stress of zinc deficiency. J Biol Chem 282:2184-95
Bird AJ, Swierczek S, Qiao W, Eide DJ, and Winge DR (2006) Zinc metalloregulation of the zinc finger pair domain. J Biol Chem 281:25326-35
Qiao W, Mooney M, Bird AJ, Winge DR, and Eide DJ (2006) Zinc binding to a regulatory zinc-sensing domain monitored in vivo by using FRET. Proc Natl Acad Sci USA 103:8674-79
Keller G, Bird AJ, and Winge DR (2005) Independent Metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae. Eukaryot cell 4:1863-71
Herbig A, Bird AJ, McCall K, Mooney M, Chang-Yi W, Eide DJ, and Winge DR (2005) Zap1 activation domain I and its role in controlling gene expression in response to cellular zinc status. Mol Microbiology 57:834-46
Bird AJ, Blankman E, Stillman DJ, Eide DJ, and Winge DR (2004) The Zap1 transcriptional activator also acts as a rpressor by binding downstream of the TATA box in ZRT2. EMBO J 23:1123-1132
Rutherford JC and AJ Bird (2004) Metal-responsive transcription factors that regulate iron, zinc and copper homeostasis in eukaryotic cells. Eukaryot Cell 3:1-13
Bird AJ, McCall K, Kramer M, Blankman E, Winge DR, and Eide DJ (2003) Zinc fingers act as Zn2+ sensors for regulation of activation domain function in the yeast Zap1 transcriptional activator. EMBO J 22:1-10
Evans-Galea M, Blankman E, Myszka D, Bird AJ, Eide DJ, and Winge DR (2002) Two of the five zinc fingers in the Zn-regulated Zap1 transcription factor dominate site-specific DNA binding. Biochemistry 42:1053-1061
Bird AJ, Zhao H, Luo H, Jenson LT, Srinivasan C, Evans-Galea M, Winge DR, and Eide DJ (2000) A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1 transcriptional activator. EMBO J 19:1-10.
Bird AJ, Evans-Galea M, Blankman E, Zhao H, Luo H, Winge DR, and Eide DJ (2000) Mapping the DNA binding domain of the Zap1 zinc-responsive transcriptional activator. J Biol Chem 275:16160-16166
Bird AJ, Turner-Cavet JS, Lakey JH, and Robinson NJ (1997) A carboxyl-terminal Cys2/His2-type zinc finger motif in DNA primase influences DNA content in Synechococcus PCC 7942. J Biol Chem 273:21246-21252