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Instant insight: What is metallomics?


08 April 2009

Amongst the '-omics' fields, metallomics is a relative newcomer. Ryszard Lobinski and colleagues at the National Research Council of France (CNRS), Pau, provide their definition

Metals are vital for biological systems. They play a role in fundamental processes from signalling and gene expression to catalysis. Every third protein is believed to require a metal cofactor, usually a transition metal such as copper, iron, zinc or molybdenum. These proteins include metallothionein, crucial in maintaining the body's equilibrium and in detoxification processes, metallochaperones, which protect and direct metal ions through the cell, and extracellular proteins albumin and transferrin - essential for metal transport in human blood. Metal ions are also responsible for controlling the expression of these proteins in cells. 

A schematic showing metal ions interacting with genes, proteins and metabolites

Metal ions play an essential role in the body where they interact with genes, proteins and metabolites

"Given the essential roles of metals and their implications in disease, understanding the mechanisms involved in these processes is of paramount importance. This is where metallomics will help"
As some metals are crucial for the body to function, not having enough of these elements can result in disease. But so too can the excessive presence of others: for example, arsenic, chromium and nickel have been linked to cancer and immune system malfunction, mercury to foetal death or malformation, and aluminium, mercury and manganese to neurological disorders. 

Organisms sense and store metals and manufacture metal-containing enzyme active sites in response to environmental signals and stress. Given the essential roles of metals and their implications in disease, understanding the mechanisms involved in these processes is of paramount importance. This is where 'metallomics' will help. 

As scientists have decoded the complete genetic blueprints of an increasing number of organisms, many different '-omics' disciplines have emerged. The aim of these is to analyse a particular class of components of a living organism. 

The first of these to develop was genomics, the study of the full set of an organism's genes: the genome. The genome contains information that allows us to predict the primary sequences of all proteins which can be (but not necessarily are!) expressed. The discrepancy between proteins that can be and proteins that are made is the fundament of another '-omics' discipline: proteomics. This is the study of the complete set of proteins produced in a cell, tissue or organism, their localisation, structure, stability, and interaction. 

Proteomics has gone through an exponential development in the past decade, made possible by the invention of soft ionisation mass spectrometry (MS) techniques. Advances in molecular MS are also at the origin of the spectacular progress of metabolomics - the study of the entire set of metabolites of an organism. 

But the analytical approaches to proteomics and metabolomics usually ignore the existence of metal complexes with proteins and metabolites. Information on the metal-biomolecule interactions is either lost during ionisation MS, during sample preparation (because of denaturation) or simply not acquired because of the inadequate ionisation efficiency, and, consequently, insufficient sensitivity. Yet cell chemistry needs to be characterised not only by its DNA, proteins and metabolites, but also by the metallome - the distribution of metals and metalloids among the different species and cell compartments.

"Metallomics is the systematic study of metallomes and the interactions and functional connections of metal ions and their species with genes, proteins, metabolites and other biomolecules within organisms and ecosystems."
Metallomics is the systematic study of metallomes and the interactions and functional connections of metal ions and their species with genes, proteins, metabolites and other biomolecules within organisms and ecosystems. Characterising  metallomes, and their interactions, requires dedicated analytical approaches to detect, locate, identify and quantify metal species, as well as revealing their function in the body. The ultimate goal of metallomics is to provide a global and systematic understanding of the metal uptake, trafficking, role and excretion in biological systems, potentially to be able to predict all of these in silico using bioinformatics. 

Metallomics is an emerging field. As it develops, this transdisciplinary research area has the potential to impact on fields from biogeochemistry, to clinical chemistry and pharmacology, plant and animal physiology, and nutrition. 

Read more in the critical review 'Metallomics: the concept and methodology' in Chemical Society Reviews.

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Link to journal article

Metallomics: the concept and methodology
Sandra Mounicou, Joanna Szpunar and Ryszard Lobinski, Chem. Soc. Rev., 2009, 38, 1119
DOI: 10.1039/b713633c

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