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Isotope metallomics approaches for medical research

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Abstract

Metallomics is a rapidly evolving field of bio-metal research that integrates techniques and perspectives from other “-omics” sciences (e.g. genomics, proteomics) and from research vocations further afield. Perhaps the most esoteric of this latter category has been the recent coupling of biomedicine with element and isotope geochemistry, commonly referred to as isotope metallomics. Over the course of less than two decades, isotope metallomics has produced numerous benchmark studies highlighting the use of stable metal isotope distribution in developing disease diagnostics—e.g. cancer, neurodegeneration, osteoporosis—as well as their utility in deciphering the underlying mechanisms of such diseases. These pioneering works indicate an enormous wealth of potential and provide a call to action for researchers to combine and leverage expertise and resources to create a clear and meaningful path forward. Doing so with efficacy and impact will require not only building on existing research, but also broadening collaborative networks, bolstering and deepening cross-disciplinary channels, and establishing unified and realizable objectives. The aim of this review is to briefly summarize the field and its underpinnings, provide a directory of the state of the art, outline the most encouraging paths forward, including their limitations, outlook and speculative upcoming breakthroughs, and finally to offer a vision of how to cultivate isotope metallomics for an impactful future.

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Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

Caco-2:

Heterogeneous human epithelial colorectal adenocarcinoma cell line

DXA:

Dual-energy X-ray absorptiometry

FPN:

Ferroportin

GIEC:

Gravity-driven ion exchange chromatography

HCC:

Hepatocellular carcinoma

IEC:

Ion exchange chromatography

ICP-MS:

Inductively coupled mass spectrometry

HepG2:

Human liver cells from hepatocellular carcinoma patient

HPIC:

High-performance ion chromatography

LA-ICP-MS:

Laser ablation inductively coupled mass spectrometry

LA-MC-ICP-MS:

Laser ablation multi-collector inductively coupled mass spectrometry

MC-ICP-MS:

Multi-collector inductively coupled mass spectrometry

MT:

Metallothionein

PFA:

Poly-fluoralkyl

PIEC:

Pressure-assisted ion exchange chromatography

PP:

Polypropylene

Q-ICP-MS:

Quadrupole inductively coupled mass spectrometry

SGIEC:

Sequential gravity-driven ion exchange chromatography

SVIEC:

Sequential vacuum-assisted ion exchange chromatography

SIMS:

Secondary ion mass spectrometry

SOD1:

Superoxide dismutase (form 1)

TIMS:

Thermal ionization mass spectrometry

VIEC:

Vacuum-assisted ion exchange chromatography

WD:

Wilson’s disease

XRF:

X-ray fluorescence

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Acknowledgements

The authors wish to thank Olivier Alard for his expert feedback regarding LA-MC-ICP-MS techniques. We would also like to thank our two anonymous reviewers, whose comments greatly benefited the manuscript. This research was supported by Macquarie University Deputy Vice Chancellor of Research (DVCR) discretionary funding.

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BM, RC, and ST conceptualized manuscript content. BM wrote the manuscript. RC, DP, FM, and ST assisted in revision and editing.

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Correspondence to Brandon Mahan.

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Mahan, B., Chung, R.S., Pountney, D.L. et al. Isotope metallomics approaches for medical research. Cell. Mol. Life Sci. 77, 3293–3309 (2020). https://doi.org/10.1007/s00018-020-03484-0

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