Instant insight: Metallomics

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E2S: Energy and Environment Solutions
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Instant insight: Metallomics

Metallomics is an emerging discipline within bioinorganic chemistry, with applications in biology and medecine. UPPA researchers from IPREM have played an important role in the development of this field.

Metal ions play a vital role in fundamental processes such as signalling, gene expression, and catalysis utilised in biological systems. Insufficient levels of some metals result in disease, whereas the presence of others has frequently been evoked in the context of carcino- (As, Cr, Pt), immuno- (Au, Co, Cr, Ni, Pt), embryo-/terato- (Hg), spermio- (Cd,Pb, Tl), nephro- (Cd, U) or neurotoxicity (Al, Hg, Mn). Every third protein is believed to require a metal cofactor, usually a transition metal, such as e.g. Cu, Fe, Zn or Mo. Metal ions control up- and down-regulation of protein expression in cells: some proteins, e.g. metallothionein, are crucial in homeostasis and detoxication processes. Metallochaperones protect and direct metal ions through the cytoplasm while extracellular albumin and transferrin are essential metallotransporters in human blood. The understanding of mechanisms by which an organism senses and stores metals and manufactures metal-containing active sites as a function of environmental signals and stress is of paramount importance. The chemistry of a cell needs to be characterized not only by its characteristic genome in the nucleus and the set of proteins present (proteome), but also by the distribution of the metals and metalloids among the different species and cell compartments, the metallome.

The knowledge of the complete genetic blueprint of the increasing number of organisms has resulted in the emergence of different “-omics”, the disciplines aiming at the analysis of a particular class of components of a living organisms in its ensemble. The genome of an organism contains information allowing the prediction of the entirety of the primary sequences of proteins which can (but not necessarily are!) expressed. This fact is the fundament of proteomics, the study of the complete set of proteins produced in a cell, tissue or organism, their localisation, structure, stability, and interaction. The exponential development of proteomics in the recent decade became possible owing to the invention of soft ionization MS techniques, using electrospray and matrix-assisted laser desorption (MALDI) ionization. Advances in molecular mass spectrometry are also at the origin of the spectacular progress of metabolomics (the study of the entire set of metabolites of an organism).

The canonical analytical approaches to proteomics and metabolomics usually ignore the existence of metal complexes with proteins and metabolites. The information on the metal-biomolecule interactions is either lost during ionization (e.g. MALDI), on the level of sample preparation (because of denaturation) or simply not acquired because of the inadequate ionization efficiency, and, consequently, insufficient sensitivity. The characterization of the metallomes, and of their interactions with the genome, transcriptome, proteome and metabolome requires dedicated analytical approaches to in vivo detection, localisation, identification and quantification, in vitro functional analysis and in silico prediction using bioinformatics.

Metallomics is a systematic study of a metallome, interactions and functional connections of metal ions and their species with genes, proteins, metabolites and other biomolecules within organisms and ecosystems. Its ultimate goal is to provide a global and systematic understanding of the metal uptake, trafficking, role and excretion in biological systems. It is a transdisciplinary research area with an impact on biogeochemistry, clinical chemistry and pharmacology, plant and animal physiology, and nutrition.