Deborah B. Zamble

Deborah B. Zamble


BSc, University of Toronto, 1993
PhD, M.I.T., 1999
Postdoc, Harvard Medical School, 1999-2001

Address LM443
80 St. George St.
Toronto, ON M5S 3H6
Lab Zamble Lab
Lab Phone 416-946-8021
Office Phone 416-978-3568

Deborah B. Zamble grew up in Kingston, Ontario.  She graduated with a B.Sc. in Biochemistry and Chemistry from the University of Toronto, studying zinc-finger proteins for her undergraduate thesis in the lab of Prof. B. Sarkar.  She earned a Ph.D. in 1999 in Biological Chemistry at M. I. T., where she worked under the guidance of Stephen J. Lippard on the mechanism of action of the anticancer drug cisplatin.  This research examined the activity of the nucleotide excision repair pathway on the different types of cisplatin-DNA cross-links, and the role of p53 in the cellular response to the drug.  Deborah then moved across the river to work as an NIH Postdoctoral Fellow with Christopher T. Walsh at Harvard Medical School, studying the zinc-containing protein component of the antibiotic  Microcin B17 synthetase.

In 2001 Deborah moved back to the University of Toronto, where her lab examines how bacteria handle transition metal nutrients.  In particular, the focus is on the use of nickel by pathogenic microorganisms, including uptake, storage, distribution and genetic regulation.

Research Lab

In the Zamble lab we are studying the rules and requirements that govern intracellular transition homeostasis at a molecular level, with a particular focus on nickel biochemistry. Trainees who join the lab come from a wide variety of backgrounds, and the learn to apply a multidisciplinary approach to study this fundamental aspect of life. We use methods drawn from fields such as biochemistry, microbiology, structural biology, and inorganic chemistry.

Learn more: Zamble Lab

Research Description


We are interested in how transition metals are recognized and handled in vivo.

It is clear that transition metals are essential structural and catalytic components of biological systems, providing a chemical versatility that is not otherwise available.  However, these elements are also quite toxic and can cause a lot of damage to cells if they are allowed to accumulate in an unregulated and unprotected fashion.  Nature solves this problem through the activity of specialized metalloproteins that strictly control the use of each metal.  These proteins function to import each type of metal, deliver the ions to the locations in the cell where they are used or stored, and detoxify and remove excess metals.  Furthermore, these systems are regulated at the genetic level, typically by metal-responsive transcription factors.  At this time, we don’t understand the mechanism of action of these systems or how they are coordinated.  Knowledge about this fundamental aspect of life has multiple applications in nutrition, medicine, and environmental protection.

Our experiments are designed to address several specific questions:

  1. What are the protein factors involved?  What is the physiological role of these proteins?
  2. Do the proteins bind metals?  If so, which ones and how much?  What do the protein-metal complexes look like?
  3. How is metal specificity achieved?  For example, why does a nickel-containing enzyme only contain nickel?  How is it possible that other metals present in the cell, such as copper, iron, or zinc, are not incorporated into the enzyme?
  4. How do the proteins respond to the metals?  Does metal binding activate allosteric conformational changes in the proteins?  Do these changes send a biochemical signal to other factors in the cell?
  5. What is the mechanism of metal transfer between proteins?  Our working hypothesis is that many types of metal ions are not allowed to float around unprotected in the cytosol of cells, given that they can cause damage (i.e. to DNA or other molecules).  We believe that metals are carried around the cell bound to specific proteins, but we don’t know how the ions are directly transferred from one protein to another.

Systems Under Investigation

To address these questions and define the biochemical mechanisms of transition metal homeostasis we are studying the proteins from several connected nickel pathways as well as their cellular activities.  These systems include a nickel-responsive transcription factor called NikR and the pathway responsible for hydrogenase enzyme biosynthesis.   We examine the biochemical activities of the purified proteins in solution, as well as their biological activities within a cellular context.  Most of the pathways are from bacteria such as Escherichia coli and Helicbacter pylori.

Awards & Distinctions

2009-2012 — NSERC Discovery Accelerator Research Award
2007-2009 — Alfred P. Sloan Research Fellow
2006 — Faculty of Arts and Science Outstanding Teaching Award
2001-2010 — Canada Research Chair in Metallobiochemistry
2002-2006 — Premiers Research Excellence Award

Courses Taught

BCH473Y Advanced Research Project in Biochemistry


View all publications on PubMed

Relationship between Ni(II) and Zn(II) coordination and nucleotide binding by Helicobacter pylori [NiFe]-hydrogenase and urease maturation factor HypB
A. M. Sydor, H. Lebrette, R. Ariyakumaran, C. Cavazza, D. B. Zamble
J. Biol. Chem. (2014) 289, 3828-3841.  Read

Metal transfer within the Escherichia coli HypB-HypA complex of hydrogenase accessory proteins
C. D. Douglas, T. T. Ngu, H. Kaluarachchi, D. B. Zamble
Biochemistry (2013) 52, 6030-6039.  Read

Metal-binding properties of Escherichia coli YjiA, a member of the metal homeostasis-associated COG0523 Family of GTPases
A. M. Sydor, M. Jost, K. S. Ryan, K. E. Turo, C. D. Douglas, C. L. Drennan*, D. B. Zamble
Biochemistry (2013) 52, 1788- 1801.  Read

Non-Specific Interactions Between Escherichia coli NikR and DNA are Critical for Nickel-Activated DNA Binding
S. Krecisz, M. D. Jones, D. B. Zamble
Biochemistry (2012) 51, 7873-7879.  Read

YeiR: A metal-binding GTPase from E. coli involved in metal homeostasis
C. E. Blaby-Haas, J. A. Flood, V. de Crécy-Lagard*, D. B. Zamble
Metallomics (2012) 4, 488-497.  Read

The metal selectivity of a short peptide maquette imitating the high-affinity metal-binding site of E. coli HypB
C. D. Douglas, A. V. Dias, D. B. Zamble
Dalton Trans. (2012) 41, 7876-7878.  Read

Nickel binding and [NiFe]-hydrogenase maturation by the metallochaperone SlyD with a single metal-binding site in Escherichia coli
H. Kaluarachchi, M. Altenstein, S. R. Sugumar, J. Balbach, D. B. Zamble
J. Mol. Biol. (2012) 417, 28-35.  Read

Protein interactions and localization of Escherichia coli HypA during nickel insertion to [NiFe] hydrogenase
K. C. Chan Chung, D. B. Zamble
J. Biol. Chem. (2011) 286, 43081-43090.  Read

Effects of metal on the biochemical properties of Helicobacter pylori HypB, a maturation factor of [NiFe]-hydrogenase and urease
A. M. Sydor, J. Liu, D. B. Zamble
J. Bact. (2011) 193, 1359-1368.  Read