Research Interests:

Research in the Bird lab focuses on metal ion homeostasis in eukaryotic cells.  Metal ions 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 how 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 metal ions in the cytosol for normal cellular metabolism. To gain insight into this universal process we use the fission yeast Schizosaccharomyces pombe as a model system.

Current research questions that we are addressing include:

1. How are eukaryotic cells able to sense changes in levels of labile zinc ions in the cytoplasm?  In fission yeast we have found that a transcription factor called Loz1 plays an essential role in sensing zinc ion availability.  In collaboration with Dr. Mark Foster (OSU Chemistry and Biochemistry) we are testing whether Loz1 is able to directly sense zinc ion availability using a pair of specialized zinc finger domains.  

2. How do cells maintain zinc homeostasis?  In addition to Loz1-dependent changes in gene expression, we have found that some genes are regulated by zinc in a Loz1-independent manner.  We are identifying the regulatory factors involved in this process and are determining how nutrient-dependent changes in gene expression allow cells to maintain zinc homeostasis.

3. How are zinc levels inside of organelles regulated?  In all eukaryotes, proteins belonging the ZIP and CDF families transport zinc ions into and out of the cytoplasm, respectively.  We are studying how cells regulate the flux of zinc ions through these proteins to gain a better understanding of how the levels of zinc inside of compartments are controlled.

Publications:

• Bird AJ and Wilson S (2020). Zinc homeostasis in the secretory pathway in yeast. Curr Opin Chem Biol 55:145-150.

• Wilson S, Liu YH, Cardona-Soto C, Wadhwa V, Foster MP, and Bird AJ (2019). The Loz1 transcription factor from Schizosaccharomyces pombe binds to Loz1 response elements and represses gene expression when zinc is in excess. Mol Microbiol 112:1701-1717.

• Hu Y-M, Boehm DM, Chung H, Wilson S, and Bird AJ (2019) Zinc-dependent activation of the Pho8 alkaline phosphatase in Schizosaccharomyces pombe. J Biol Chem 294:12392-12404.

• 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