Editorial “metallomics: emerging investigators”

In this issue, we highlight the exciting work a few emerging investigators are doing in the field of metallomics. Perhaps because metallomics is itself an emerging field, young investigators are having a powerful impact.

Metallomics shares with other emerging fields—including genomics, proteomics, and neuroscience—an interest in understanding big pictures and complex wholes. For that reason, metallomics requires a systematic approach and the desire and ability to integrate information, often across disparate fields. Integration often requires researchers to take an interdisciplinary approach. The scope of Metallomics—the journal—makes clear the interdisciplinary nature of the field.

Metallomics touches on many areas of science that profoundly impact society, including biogeochemistry and environmental chemistry, clinical chemistry and pharmacology, and nutrition and health.¹ For many younger scientists, its focus on issues of social importance adds to its appeal.

As with all attempts to study complex phenomena, a big part of the challenge is, you might say, epistemological. It's about understanding what it means to know something and how that might be achieved: how to measure something against a complex background, or how to think about and express what is occurring in a dynamic setting. This is difficult work, and it requires new tools that have undergone rigorous testing and a critical examination of how they function. Analytical chemistry and imaging have featured prominently in many of the articles this journal has published. Several of the emerging investigators featured in this issue are developing new methodologies with which to study the metallome.

The Royal Society of Chemistry and RSC Publishing places much value in encouraging younger researchers and promoting their work, as can be seen from the many Emerging and Young Investigator themed issues across RSC journals, including Chemical Communications and Journal of Analytical Atomic Spectrometry. In this issue, Metallomics has taken the opportunity to recognize an emerging generation of scientists.

While emerging scientists are the special focus of this issue, presenting their work is nothing new for Metallomics, which has published exciting work from young investigators throughout its nearly 4-year history. This issue only captures a small snapshot of that work. While we had no firm criteria for distinguishing between emerging and established scientists, we have focused primarily on investigators in the first 10 years of their independent careers.

This issue includes articles from the following researchers.

Lydia Finney is an assistant physicist and biochemist at the advanced photon source (APS) at Argonne National Labs, working to make X-ray fluorescence imaging more accessible to bioinorganic chemists. She received her PhD in inorganic chemistry from Northwestern University in 2005. In 2004 she was named a Hertz Fellow by the Hertz Foundation. Her contribution to this issue, “Identifying metalloproteins through X-ray fluoresence mapping and mass spectrometry,” illustrates how technical developments in imaging and microscopy are providing new insights into the metallome. This is her first contribution to Metallomics.
Katherine (Kathy) Franz is an associate professor of chemistry at Duke University. Appointed in 2003, she and her lab have since focused on developing prochelators, molecules that can chelate metal ions after a chemical transformation, which ideally can be triggered at the site where binding is desired. Her lab has also done a lot of work to understand mechanisms of copper uptake in cells and to utilize knowledge of copper binding motifs to develop copper probes. She was the recipient of the Camille Dreyfus Teacher-Scholar Award in 2009, an Alfred P. Sloan Research Fellow in 2008, an ACS PROGRESS/Dreyfus Lectureship Award in 2007, and an NSF CAREER Award in 2005.

Franz's paper “Prochelator BHAPI protects cells against paraquat-induced damage by ROS-triggered iron chelation” describes the in vivo utilization of a prochelator to bind iron after activation by hydrogen peroxide. This single molecule can thereby act both as an antioxidant and as a chelator for metal ions, and prevent two potentially detrimental chemical species from reacting. This molecule does not bind iron in its prochelator form, so it does not induce iron deficiency in healthy cells.

Kathy has published in Metallomics two other papers, which report some of her work on the cellular biology of copper, including “Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein 1” (Metallomics, 2010, 2, 74–83) and “A comparison of methionine, histidine and cysteine in copper(I)-binding peptides reveals differences relevant to copper uptake by organisms in diverse environments” (Metallomics, 2011, 3, 61–73).

Martin Högbom is an associate professor in the Department of Biochemistry and Biophysics at Stockholm University. At the 10th EUROBIC meeting, he received the European Medal for Bioinorganic Chemistry, which since 2008 has been designated for young or mid-career scientists. He is also a member of the Young Academy of Sweden. He was designated a “Future Research Leader” by the Swedish Foundation for Strategic Research, and he received the Ruth and Nils-Erik Stenback award for research, awarded by the Finnish Society of Sciences and Letters.

His paper, “X-ray reduction correlates with soaking accessibility as judged from four non-crystallographically related diiron sites,” draws attention to the challenges of assigning oxidation states – a critical piece of information for any metalloprotein – from X-ray data, and provides evidence to support the hypothesis that solvent accessibility is correlated with ease of photoreduction. This paper is a follow-up to his 2011 review article, “Metal use in ribonnucelotide reductase R2, di-iron, di-manganese and heterodinculear – an intricate bioinorganic workaround to use different metals for the same reaction” (Metallomics, 3, 110–120).

Tim Storr, an assistant professor of chemistry at Simon Fraser University, Canada, is a scholar of the Michael Smith Foundation for Health Research. His new research program is supported by both the Natural Sciences and Engineering Research Council of Canada and the Alzheimer’s Association.

His paper “Dual-function triazole-pyridine derivatives as inhibitors of metal-induced amyloid-β aggregation” in collaboration with Mi Hee Lim at the University of Michigan, illustrates how understanding coordination chemistry facilitates the design of ligands that can bind metals and, as demonstrated in this paper, diminish the degree of Aβ aggregation. Understanding how metal ions function in pathological conditions can facilitate bioinorganic treatment strategies. Tim has also recently contributed to a New Talent: Americas issue in Dalton Transactions.

Mi Hee Lim, an assistant professor of chemistry at the University of Michigan, won the Paul Saltman Award for rising young scientists at the Metals in Biology Gordon Research Conference in 2012 and the ACS Division of Inorganic Chemistry Young Investigator Award in 2007.

Mi Hee has previously contributed to a themed issue in Metallomics on Neurodegenerative Diseases. “Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-β aggregation” (Metallomics, 2011, 3, 284–291).

Fanis Missirlis is a cell biologist at the Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico and a member of the Junior European Drosophila Investigators. Fanis uses Drosophila to study the cellular biology of iron and to understand how iron cycling and utilization affects organismal utilization of other metals, including copper, zinc, magnesium, and molybdenum. His paper, “Genes for iron metabolism influence circadian rhythms in Drosophila melanogaster,” demonstrates a link between circadian rhythms and iron homeostasis in Drosophila melanogaster, connecting the cellular biology of iron to the diurnal cycling of metabolism. This is his first contribution to Metallomics.
Hua Naranmandura is an associate professor in the Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics in the College of Pharmaceutical Sciences and Zhejiang University, in China. He did his doctoral work at Chiba University in Japan and then a post-doctoral fellowship at the University of Alberta.

His paper, “Arsenic metabolism and thioarsenicals,” reviews what is known about arsenic metabolism and supports his hypothesis that arsenic methylation occurs via a reductive pathway in which As(III) is bound to proteins. In this novel model, oxidation to As(V) is thought to occur when As is released from proteins, and occurs only during the final step of arsenic metabolism.

Some earlier work on arsenic metabolism was reported in a 2011 Metallomics paper, “Generation of thioarsenicals is dependent on the enterohepatic circulation in rats” (Metallomics, 2011, 3, 1064–1073).

Elizabeth Nolan is an assistant professor of chemistry at MIT. She began her independent career there in 2009, and in 2010 received an NIH New Innovator Award and was named a Searle Scholar in 2011.

Her paper, “Siderophore-based detection of Fe(III) and microbial pathogens,” shows scientists how to exploit the exquisite sensitivity with which siderophores bind iron—and receptors bind siderophores—to develop platforms for fluorescence-based iron detection and pathogen sensing. She is a first-time contributor to Metallomics.

All these papers ask bold questions and engage difficult issues, and the courage of these scientists to take them on is inspiring. This field offers many exciting opportunities to investigators at various stages of their careers, if they are willing to think about in a systems-focused way and to do the careful work required to extract meaningful information from complex and often data-intensive experiments. Metallomics is delighted to provide a visible home for these compelling new investigations and investigators.

Professor Rachel Austin, Bates College, USA.

Editorial Board member, Metallomics.

References

1. R. Lobinski, J. Sabine Becker, H. Haraguchiand and B. Sarkar, Pure Appl. Chem., 2010, 82, 493–504.

---