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Deborah Zamble

Deborah Zamble

Academic Title: Professor

Phone: 416-978-3568

Office: DB 443

Email:

Research Homepage: https://sites.chem.utoronto.ca/zamblelab/

Research

In the field of bioinorganic chemistry the principles of inorganic, organic and biological chemistry are applied to study metals in biological systems.  This area is rapidly expanding due to recent advances in inorganic spectroscopy, genetics, molecular biology and structural biology.  We are now poised to answer some interesting and fundamental questions about intracellular metal homeostasis.  In this lab, we are investigating several biological pathways containing metalloproteins with a focus on the metal sites.  

Transition metals play an essential role in biological systems but they also have toxic properties.  To be able to use the rich chemistry of transition metals, cells have developed pathways for specific metal uptake, transfer within the cell, storage, detoxification, and export.  These pathways must all be tightly regulated so that the appropriate metals are available when required but unprotected pools of these potentially toxic nutrients do not accumulate.  An understanding of metal homeostasis requires identification of the proteins involved, as well as research into the mechanisms of regulation, specific metal recognition, and metal transfer.

Applications.  Aside from fundamental studies into the chemistry of biological systems, this research has many broad implications.  Medical applications include the design of antibiotics that target the unique metal requirements of microorganisms;  and in human nutrition and in the prevention and treatment of diseases related to metal homeostasis.  These studies will also provide information that can be used to engineer organisms as biosensors or for bioremediation, an area that is growing in importance with the increase in environmental pollution.  

Tools Biological chemistry, and in particular bioinorganic chemistry, is inherently multidisciplinary.  Scientists in this field apply methodology from a wide variety of fields.  Many techniques will be used in this lab including protein expression and purification, gene cloning and mutagenesis, in vitro biochemical assays and spectroscopy.  Some types of experiments, such as structural analysis and certain types of inorganic spectroscopy, will involve collaborations with other labs.

Nickel biochemistry.  Several projects in this lab will investigate nickel pathways in the bacteria E. coli.  It is now known that there are multiple metalloenzymes that contain nickel, and that this element has an essential role in both prokaryotes and eukaryotes.  The mechanism of metallocenter assembly in nickel-containing enzymes involves accessory proteins that somehow put nickel atoms into the correct protein to produce active enzyme.  It is not clear how this happens, or how metal specificity is achieved and these are the questions that will be addressed.  Other projects in this area include identification and characterization of proteins that transfer nickel within the cell, and the mechanism of nickel-specific regulation at the genetic level.

Metal Specificity.  Another area of research involves the mechanism of metal specificity.  Proteins that regulate metal homeostasis, such as transcription factors, are able to respond specifically to one metal even in the presence of other metals.  Furthermore, these proteins can differentiate between the appropriate metal and all of the other metals that are present in the cellular environment, some at much higher concentrations.  The properties required for metal specificity will be investigated by using a family of transcription factors that have the same function and activity, but that are specific for different transition metals, such as zinc, mercury, copper and cobalt.  

Selected Publications

See Research Homepage