Keynote Speakers

A diverse line up of exceptional experts shaping the forefront of metallomics.

Session: Theoretical & Applied Bioinorganic Chemistry

Aitziber Lopez Cortajarena

Prof. Aitziber Cortajarena earned her Ph.D. in Biochemistry from the Universidad del País Vasco in2002. Then, she worked on protein design in the group of Dr. Lynne Regan at Yale University, USA, as a Postdoctoral and Associate Research Scientist. She joined IMDEA Nanociencia in 2010 and started her independent research in nanobiotechnology. In 2016, she joined CIC biomaGUNE as Ikerbasque Research Professor where she leads the Biomolecular Nanotechnology group and is ScientificDirector since 2022.

Her work has been recognized by the Horizon Prize from The Royal Society of Chemistry, the Research Excellence Award from The Spanish Royal Society of Chemistry, and the Women in Science Career Award from Ikerbasque. In 2023, she was elected member of the Spanish Royal Academy of Science. She is Senior Editor at Protein Science. She is Vice president of the Spanish Biophysical Society, Secretary of the Chemical Biology Group form the RSEQ, and Past-Member of the International Protein Society Council. Cortajarena has obtained numerous European projects, including an ERC Consolidator Grant, two ERC-PoC, an ERA-CoBioTech, four FET-Open projects, and one EIC Pathfinder project, which cover from the fundamental development of protein-based tools to the validation of biomolecule-based technologies in biomedical and technological applications.

Abstract

ENGINEERED BIO-METALLIC COMPOSITES: NOVEL BIOMEDICAL AND TECHNOLOGICAL TOOLS

A. Lopez Cortajarena
Biomolecular Nanotechnology, CIC biomaGUNE-BRTA, San Sebastián, Spain

Inspired by nature, we explore biomolecules and their derivatives as novel biomedical and technological tools. Among biomolecules, proteins rise huge interest due to their high structural and functional versatility, biocompatibility, and biodegradability. In particular, we mainly focus on a class of engineered repeat proteins, due to their stability and robustness as a base scaffold that can be easily tailored to endow desired functions to the protein and to encode defined supramolecular assembly properties. For example, the introduction of metal-binding residues (e.g., histidines, cysteines) drives the coordination of metal ions and the subsequent formation of tailored metallic nanomaterials [1,2]. These properties allow the development of protein-nanomaterial composites [3,4]. Generally, the fusion of two distinct materials exploits the best properties of each, however, in bio-metallic composites, the fusion takes on a new dimension as new properties arise.

These composites have ushered the use of protein-based metal nanomaterials as biopharmaceuticals beyond their original therapeutic scope and paved the way for their use as theranostic agents, as demonstrated in our pioneering in vitro and in vivo examples. [3,4] In addition, these protein hybrids can be also implemented in technological applications, towards protein-based bioelectronic and catalytic materials [5,6,7].

Scheme of engineered protein-metal composites and potential applications.

 

References: 

  1. E. Lopez-Martinez, D. Gianolio, S. Garcia-Orrit, V. Vega-Mayoral, J. Cabanillas-Gonzalez, C. Sanchez-Cano, A. L. Cortajarena. Adv. Optical Mater., 2022, 10, 2101332. 
  2. A. Aires, Y. Fernández-Afonso, G. Guedes, E. Guisasola, L. Gutiérrez, A. L. Cortajarena. Chem. Mater., 2022, 34, 10832–10841.
  3. A. Aires, D. Maestro, J. Ruiz del Rio, A. R. Palanca, E. Lopez-Martinez, I. Llarena, K. Geraki, C. Sanchez-Cano, A. V. Villar, A. L. Cortajarena. Chem. Sci., 2021, 12, 2480-2487.
  4. K. B. Uribe, E. Guisasola, A. Aires, E. López-Martínez, G. Guedes, I. R. Sasselli, A. L. Cortajarena. Acc. Chem. Res., 2021, 54, 4166-4177.
  5. S. H. Mejias, E. López-Martínez, M. Fernandez, P. Couleaud, A. Martin-Lasanta, D. Romera, A. Sanchez-Iglesias, S. Casado, M. R. Osorio, J. M. Abad, M. Teresa González, A. L. Cortajarena. Nanoscale, 2021, 13, 6772-6779. 
  6. A. Dominguez-Alfaro, N. Casado, M. Fernandez, A. Garcia-Esnaola, J. Calvo, D. Mantione, M. Reyes Calvo, A. L. Cortajarena. Small, 2023, 13, 2307536.
  7. R. López-Domene, S. Vázquez-Díaz, E. Modin, A. Beloqui, A. L. Cortajarena. Adv. Funct. Mater., 2023, 33, 2301131.

Artur Krężel

Artur Krężel is Professor of Biological Sciences and Department Chair of Biological Chemistry at the University of Wrocław (Poland). He received his diploma in chemistry (Master of Science, 2000) and a Ph.D. degree in bioinorganic chemistry (2004) from the University of Wroclaw, Poland, under the supervision of Prof. Wojciech Bal. During his postdoctoral training (2004-2007) at the University of Texas Medical Branch in Galveston, he worked with Prof. Wolfgang Maret on mechanisms of cellular zinc homeostasis, which bore fruit in discovering metallothioneins as physiological zinc ion buffers. He then accepted a position as an assistant professor at the Faculty of Biotechnology of his alma mater. In 2011, he received a D.Sc. degree from his university.


Currently, he is a full professor and head of the Department of Chemical Biology. His research concentrates on several areas at the interface of inorganic biochemistry, biophysics, and chemical biology, particularly understanding the molecular bases of zinc and copper metabolism. Examples of this endeavour are structure-function relationships, the stability of metalloproteins, protein folding and thermodynamics, and the development of new analytical methods, such as fluorescent probes for selective protein modifications and metal sensing, mass spectrometry approaches for studying metalloproteins(un)folding and structures.

Abstract

AN INTEGRATED APPROACH UTILIZING SPECTROSCOPIES, MASS SPECTROMETRY, AND MOLECULAR DYNAMICS SIMULATIONS FOR STUDYING CELLULAR ZINC BUFFERING PROPERTIES OF METALLOTHIONEINS

A. Krężel
Department of Chemical Biology, Faculty of Biotechnology, University of Wroclaw, Wrocław, Poland

Mammalian metallothioneins (MTs) constitute a group of cysteine-rich proteins binding metal ions in two α- and β-domains, serving as a crucial cellular Zn(II)/Cu(I) buffering system. At cellular free Zn(II) concentrations (10-11-10-9 M), MTs are not fully loaded; instead, they exist as partially metal-depleted species due to their Zn(II) binding affinities within the nano- to picomolar range, matching concentrations of cellular free Zn(II).

Despite the importance of MTs, their mode of action remains poorly understood. This study aims to characterize the mechanism of Zn(II) (un)binding to MTs from various sources (mammals, animals, plants, and bacteria), elucidate the thermodynamic properties of the partially metal-depleted species, and investigate their mechanostability properties.

The study employed a combination of spectroscopic and stability studies, native mass spectrometry (MS), and label-free quantitative bottom-up and top-down MS, as well as ion mobility coupled with molecular dynamics simulations. They unravel the coordination of Zn(II) in MT species and explain differences in Zn(II) binding affinities.

The research demonstrated significant differences in protein folding and the thermodynamics of Zn(II) ion (un)binding between isolated domains and the entire protein. The proximity of domains reduced their degrees of freedom, rendering them less dynamic. Furthermore, variations in the degree of water participation in MT (un)folding impacted the differentiation of Zn(II) binding sites. The energetic consequences of domain connection critically influence the role of MTs in the cellular environment. Beyond serving as a zinc sponge, MTs function as a zinc buffering system, maintaining free Zn(II) at appropriate concentrations.

The presence of weak, moderate, and tight Zn(II) binding sites is linked to the folding mechanisms and internal electrostatic interactions of MTs. The differentiated affinities of various MTs define their zinc buffering capacity, which is essential for Zn(II) donation and acceptance at different free Zn(II) concentrations.
This research was supported by the National Science Centre of Poland (NCN) under Opus grant no. 2021/43/B/NZ1/02961.

Session: Diagnostics & Therapeutics

Cinzia Imberti

After completing her M.Sci degree in Chemistry at the University of Padova (Italy), Dr Imberti moved to the UK to undertake a MRes/PhD at King’s College London, working on the development of radiometal-based radiopharmaceuticals under the supervision of Prof. Phil Blower. In 2018, she was awarded a Sir Henry Wellcome Fellowship to study the mechanism of action of metal-based anticancer agents in the group of Prof. Peter Sadler (University of Warwick). She then joined Dr Jason Lewis’ group at Memorial Sloan Kettering Cancer Centre (New York) as a Research Associate investigating antibody-based imaging agents. In 2023 she moved to Bayer (Berlin) as a Research Scientist developing novel metal-based radiotherapies.

Dr Imberti has been awarded a UKRI FLF fellowship to lead her research group at King’s College London. Her research aims to clarify roles and behaviour of metal species–including both essential trace metals and metallodrugs–in cancer, by using a unique toolbox of multi-scale imaging techniques, such as radionuclide imaging, synchrotron X-ray Absorption and Fluorescence and laser-ablation ICP-Mass Spectrometry.

Abstract

IMAGING METALLOMICS - PICTURING METAL BEHAVIOUR IN CANCER (AND BEYOND)

C. Imberti

Imaging Chemistry and Biology, King’s College London, London, UK

Metal ions play irreplaceable roles in life as essential protein cofactors and as signalling molecules in countless biological processes. Recent advances in cell biology and physiology are revealing the vital role of endogenous metals in the progression of cancer and other diseases. Non-endogenous metals are also of interest, as they often display high toxicity, which can be harnessed in metallodrugs.

Despite the importance of metals in biology and medicine and renewed interest in the field, the low endogenous concentrations of many trace metals, and the complexity of metal behaviour in biological systems, have often hindered our ability to investigate the mechanisms regulating metal homeostasis (and how they are disrupted in disease states) and as well as the mode of action of drugs either based on metals or that exert their action by influencing endogenous metal trafficking.

However, In recent years, technical advances have extended the scope of metal-specific analytical techniques, such as laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron X-ray fluorescence (XRF) to very diluted samples such as biological systems. In addition, availability of metallic radioisotopes (such as 52Mn, 62Zn, 63Zn, 64Cu, 195mPt) with emission properties useful for imaging via positron emission tomography (PET) or single-photon emission computed tomography (SPECT) has drastically increased in the last decade.

In this talk, I will highlight recent examples of how our group has been using cutting-edge imaging techniques to research the behaviour of endogenous metals and metallodrugs in cancer models, both in cells and in vivo.

Lawrence Bernstein

Lawrence R. Bernstein received B.A. and M.A. degrees from Harvard and a Ph.D. from Stanford. His early research focused on the physical chemistry of minerals and on metal geochemistry. Over the years, his focus shifted towards metal biochemistry and metal-based therapeutics, fields in which he found he could usefully apply his geochemical and mineralogical knowledge. In particular, he has sought to develop metal-based compounds intended for the treatment of cancer, infectious disease, inflammation, and pain. Much of his recent research has focused on the biochemistry and medicinal chemistry of gallium. This research has led to the development of some new therapeutic gallium compounds, including gallium maltolate, which was designed for oral or topical administration and is currently in clinical trials.

Abstract

DEVELOPMENT OF GALLIUM MALTOLATE AS A THERAPEUTIC AGENT

L. Bernstein

Research, Gallixa LLC, Menlo Park, California, US

Therapeutic activity for gallium has been known since at least 1931, when gallium salts were found to be effective against Treponema (syphilis) and Trypanosoma infections in animals. Subsequent preclinical and clinical research has found gallium to be active against other infections, cancer, pathologic bone resorption, inflammation, and pain. Gallium’s therapeutic activity stems primarily from Ga3+ acting as a mimic of Fe3+, but with Ga lacking the redox potential of Fe under physiological conditions. The activity of gallium against pathogens or cancer results mainly from inhibition of DNA synthesis, caused by Ga3+ competing with Fe3+ and substituting for it in the active site of ribonucleotide reductase, as well as by Ga3+ binding to siderophores and interfering with microbial Fe3+-sensing systems. Ga3+ also competes with Zn2+, affecting certain Zn-dependent enzymes and other Zn-dependent molecules.

Gallium maltolate (GaM) is being developed as an orally and topically administrable form of gallium. The compound is stable over a pH range of about 5.6 – 7.8, with aqueous solubility of 24(2) mM and an octanol partition coefficient of 0.41(8) at 25°C. The oral Ga bioavailability is about 27 – 54% with an excretion half-life of about 17 – 21h. GaM is well tolerated with no reported dose-limiting toxicity at repeated doses of as much as 3500 mg/day.
Phase 1 clinical trials and compassionate use cases have demonstrated apparent efficacy, sometimes remarkable, for oral GaM in some instances of late-stage metastatic breast cancer, lung cancer, lymphoma, hepatocellular carcinoma, prostate cancer, colorectal cancer, and other cancers. Many of these cancers had been resistant to all previous therapies. In a few cases, the patient appeared to be cancer-free several years following GaM treatment. An ongoing clinical trial in refractory glioblastoma patients is showing an apparent extension of survival.

Topically administered 0.5% GaM skin cream has demonstrated apparently great efficacy in many instances of inflammatory skin disease, such as psoriasis and eczema, skin infections, skin cancers, and pain. There have been numerous patients who had severe, refractory neuropathic pain that they reported was greatly relieved by topical GaM, allowing them to discontinue their use of opioids and other powerful analgesic drugs.

Session: Biotechnology & Circular Economies

Dan Park

Dan Park is a staff scientist and group leader of the Systems and Synthetic Biology group at Lawrence Livermore National Lab, with expertise in Microbiology, Biochemistry, and Synthetic Biology. He holds degrees in Chemistry and Biochemistry from Colorado School of Mines and the University of Wisconsin, Madison. His research is focused on engineering proteins and microbial pathways for environmental applications, including recovery of clean energy critical rare earth elements, safe and stable use of genetically engineered microorganisms in the environment, and bioremediation.

Abstract

HARNESSING NATURE FOR ENHANCED RARE EARTH ELEMENT EXTRACTION AND SEPARATION

D. Park

Biosciences and Biotechnology Division, Lawrence Livermore National Lab, Livermore, USA

Rare earth element (REEs: Sc, Y, La- Lu) are irreplaceable components in many clean energy and consumer technologies. However, the extraction and subsequent separation of individual REEs from REE-bearing feedstocks remains a significant economic and environmental challenge. Here, I will discuss the development of a biology-based, all-aqueous REE extraction and separation approach as a sustainable potential alternative to conventional hydrometallurgical processes. Specifically, we are deploying lanmodulin proteins, bacterial proteins that have evolved as part of lanthanide uptake pathways and exhibit exceptionally high REE binding affinity and selectivity, for REE extraction from a range of non-traditional feedstocks (e.g., E-waste, low-grade ores, mine tailings).

We developed a method to immobilize lanmodulin onto porous resin, which facilitates the selective capture of REE ions from complex metal mixtures and enables the stable reuse over numerous extraction cycles. Using this platform, we have employed pH and chelator-driven desorption processes for intra-REE separation, including Dy/Nd separation from a range of E-waste derived mixed REE oxides, and Sc, Y, and grouped lanthanide separation from REE ore derived mixed REE oxides.

In parallel, we are developing a predictive model of lanmodulin separations to better facilitate separation process optimization and scaling. Our initial thermodynamic model captures the non-intuitive separation behavior of lanmodulin, where separation factors vary widely based on feed composition, while also accurately predicting the binding distribution of ternary, quaternary, and quinary mixtures of REE. The model also reveals intrinsic limitations of the archetypical lanmodulin that we seek to overcome through protein engineering and bioprospecting.

To this end, I’ll describe a screening platform that couples high-throughput protein purification with quantitative determination of the intra-REE selectivity profile, allowing us to screen over 900 natural and engineered REE binding proteins to date. Our screening efforts have resulted in the identification of several variants with promising intra-REE selectivity that will subjected to REE separation tests on column. Collectively, these advances bolster the prospects for using REE binding proteins as a platform for organic solvent-free REE separations.

This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DEAC52-07NA27344 (LLNL-ABS-858227).

Jason Love

Jason Love CChem FRSC is Professor of Molecular Inorganic Chemistry at the University of Edinburgh and Head of the School of Chemistry. He has published 154 peer-reviewed articles and patents, delivered over 90 international, national, and public invited lectures, including ‘Mining the Scrapheap’ at New Scientist Live (2018), and was winner of the 2020 Ekeberg Prize for his work on tantalum recycling.

His primary research interests focus on the recovery and recycling of valuable and critical metals, making use of an in-depth chemical understanding to deliver new technologies and processes. This research effort is supported by UKRI and industry funding, most recently severaliCASE awards in metal separations and an EPSRC-GCRF grant for a bilateral, multidisciplinary approach to recycle e-waste to supply valuable metals to jewellers in India and the UK.

Abstract

SUSTAINABLE CHEMISTRY FOR METAL RECYCLING

J. Love

School of Chemistry, University of Edinburgh, Edinburgh, UK

Metals are ubiquitous in modern technologies and their recycling from sources such as electronic waste, magnets, and high-performance materials is crucial to achieve circular economy and net-zero ambitions and to ensure that wastes are both minimised and environmentally benign. In this presentation, the application and significance of coordination and supramolecular chemistry in metal recycling processes will be highlighted [1-4]. New routes to the dissolution and selective separation of gold and other metals from electronic waste will be described, along with the marriage of chemical separations with biochemical remediation to ensure that effluents are environmentally benign. These case studies rationalise the need to understand the mode of action in separations processes at a fundamental chemical level and the ability to exploit ligand design to achieve new and useful separations technologies.

References:

  1. L. M. M. Kinsman, C. A. Morrison, B. T. Ngwenya, J. B. Love. Nat. Commun., 2021, 12, 6258.
  2. A. Nag, C. A. Morrison, J. B. Love. ChemSusChem, 2022, 15, e202201285.
  3. A. Nag, M. K. Singh, C. A. Morrison, J. B. Love. Angew. Chem. Int. Ed., 2023, 62, e202308356.
  4. J. G. O’Connell-Danes, B. T. Ngwenya, C. A. Morrison, J. B. Love. Nat. Commun., 2023, 13, 4497.

Kharmen Billimoria

Kharmen started her research career in 2017 undertaking a joint PhD between the National Measurement Laboratory (NML) at LGC and the Trace Metals in Medicine Group at the University of Warwick, investigating quantitative multimodal elemental imaging strategies applied to Alzheimer’s disease. Upon completing her PhD, she joined the Inorganic Analysis team at LGC, as a Researcher, primarily focussed on elemental bioimaging and solid-state analysis.

In December 2022 she was promoted to Lead Researcher for the bioimaging and single cell analysis, developing quantitative strategies in these emerging areas. In October 2023, Kharmen was granted an Honorary Research Fellowship at the University of Warwick to continue and further the collaboration between the two institutions.

Abstract

A MULTIMODAL PLATFORM FOR THE CHARACTERISATION OF ADVANCED MATERIALS

K. Billimoria

National Measurement Laboratory, LGC, Teddington, UK

Advanced and smart materials are increasingly incorporating nanotechnology into formulations to take advantage of highly efficient optical properties and scalability of this technology to be used across a wide range of applications to support the Circular Economy and Net Zero strategy. As such, there is a growing need for characterisation of both the raw nanomaterials as well as analysis of the final nanotechnology products. The challenging nature of these measurements requires a multimodal approach to support industries with bringing these new technologies to the market.

To characterise stability of light sensitive quantum dot inks used for coating electronic devices with regards to size/size distribution and elemental concentration. To use elemental maps of thin film coatings to assess defects in the production of final products.
Dynamic light scattering (DLS) measurements, along with total elemental ICPMS were used for the characterisation and determination of elemental composition, size and size distribution of the quantum dot inks. Additionally, LA-ICP-MS imaging was used to map thin films of the quantum dot inks to determine defects in the fabrication process.

The nanomaterial formulations were a combination of PbS and InAs quantum dot containing inks. DLS measurements confirmed a main population distribution of the quantum dots with sizes 10.73 ± 0.15 nm (PbS) and 13.64 ± 1.7 nm ( InAS), in addition both formulations contained a second population of agglomerated particles with a size of approximately 100 nm. Concentrations of Pb varied from 0.7-2.3 mg kg-1, whereas In and As were present at lower levels (0.27 and 0.15 mg kg-1, respectively). LA-ICP-ToF-MS imaging of the quantum dot thin film showed defects in the coating process as well as co-distribution of elements at 5 µm spatial distribution.

The characterisation of both the quantum dot ink and the final thin film products provided a meaningful insight into the robustness of their manufacturing and fabrication processes. This information was invaluable to industry to produce more robust and efficacious products in support to the circular economy.

References:

  1. L. M. M. Kinsman, C. A. Morrison, B. T. Ngwenya, J. B. Love. Nat. Commun., 2021, 12, 6258.
  2. A. Nag, C. A. Morrison, J. B. Love. ChemSusChem, 2022, 15, e202201285.
  3. A. Nag, M. K. Singh, C. A. Morrison, J. B. Love. Angew. Chem. Int. Ed., 2023, 62, e202308356.
  4. J. G. O’Connell-Danes, B. T. Ngwenya, C. A. Morrison, J. B. Love. Nat. Commun., 2023, 13, 4497.

Martin Warren

Martin Warren serves as the Chief Scientific Officer at the Quadram Institute, overseeing the formulation of the institute’s scientific strategy and leadership. His extensive expertise lies in intricate metabolic pathways, with a particular focus on tetrapyrrole biosynthesis. This molecular realm encompasses haems, chlorophylls, sirohaem, coenzyme F430, haem d1, and the corrins (such as vitamin B12). The molecular architectures of these metallo-cofactors are among the most structurally complex small molecules produced in cells, and their intricate structures are mirrored by captivating and elusive biosynthetic pathways.

By pioneering the introduction of these pathways recombinantly into systems where they were previously absent, he has been able to employ a systematic approach to their redesign for the biosynthesis of novel products. His methodology combines molecular genetics, microbiology, enzymology, and chemistry, complemented by various biophysical techniques such as NMR, EPR, and X-ray crystallography. Through these methods, he has unravelled molecular details surrounding numerous processes within the field of tetrapyrrole metabolism. In the last decade, Warren’s research has predominantly delved into vitamin B12, particularly focusing on the unique interplay between the corrin ring structure and cobalt. This interaction plays a pivotal role in facilitating the extraordinary chemistry mediated by B12-dependent processes. 

Abstract

CONTROLLING COBALT AND VITAMIN B12

M. Warren

School of Biosciences, University of Kent, Canterbury, UK

Vitamin B12 serves as the essential factor for preventing pernicious anaemia. Dorothy Hodgkin’s elucidation of its structure revealed a cobalt-containing corrin ring linked to a lower nucleotide loop. The focus of the unique chemistry facilitated by this nutrient lies in the centrally chelated cobalt within the contracted macrocycle, synthesized exclusively by a limited number of prokaryotes. Given cobalt’s general toxicity to cellular systems, there is considerable interest in understanding how bacterial cells acquire, traffic, and insert the cobalt ion into the developing B12 molecule. With the global shift towards more sustainable plant-based diets lacking B12, it becomes crucial to apply this knowledge for enhancing the commercial production of the vitamin. This improvement will enable a more extensive and cost-effective global supply of this valuable commodity.

The objective of this research is to investigate the various components associated with the uptake, transport, trafficking, and insertion of cobalt into the corrin ring within a genetically engineered E. coli strain. This strain has been modified to produce vitamin B12 through the aerobic biosynthetic pathway.


Employing an array of techniques ranging from advanced genetic and synthetic biology tools to structural biology methods like crystallography and cryoEM, we have gained significant insights into how E. coli responds to an excess of cobalt. We have elucidated the mechanisms of cobalt uptake and removal from the cell, identifying a set of importers and exporters that enable precise control over cellular cobalt acquisition. Molecular details about the trafficking and chelation of the metal into the corrin macrocycle have also been uncovered.


This comprehensive approach has led to the development of a B12-producing strain that minimizes the necessity for excessive cobalt supplementation in the culture medium. This achievement ensures a high level of cobalt uptake into the cells. Importantly, this strategy has significant implications for reducing environmental contamination in the industrial biotechnology sector.

Session: Transformative Tech & Method Development

David Clases

David Clasesis an Assistant Professor for Analytical Chemistry at the University of Graz (A). Following the award of his doctorate in 2017 at the University of Münster (GER), he became postdoctoral fellow at the University of Technology Sydney (AUS), where he was later appointed as independent lecturer. Following his return to Europe in late 2021, he founded the NanoMicroLab at the University of Graz. The NanoMicroLab focusses on the exploration of elements in small micro-and nano-scaled structures. The research team investigates and employs nanomaterials in the context of medical and biological questions and further, aims to decipher the role of natural particles as well as emerging nanoparticulate contaminants in the environment.

A current focus is set on the development and application of ICP-TOFMS for single event analyses and element mapping as well as on the driving ofnew hyphenated techniques. David gave close to 20 invited conference talks and published >40 peer-reviewed articles. He is member of the International Advisory Board of Analytical and Bioanalytical Chemistry (Springer) and was commissioning editor for Metallomics (Oxford Academics) in 2022 and2023. In 2022, he received the Division Award for analytical chemistry by the German Chemical Society (GDCh).

Abstract

OPTOFLUIDIC FORCE INDUCTION MEETS RAMAN SPECTROSCOPY AND ICP-TOFMS MOLECULAR AND ELEMENTAL SINGLE PARTICLE TECHNIQUES ARE JOINING FORCES

D. Clases1, C. Neuper1, M. Šimić1, T. E. Lockwood2, L. Schlatt3, Z. Du4, X. Xu4, H. Fitzek5, U. Hohenester6, N. Stoll7, P. D. Bohleber, Bremerhaven/GER, C. Hill8, R. Gonzalez de Vega1

1Institute of Chemistry, University of Graz, Graz, Austria
2Hyphenated Mass Spectrometry Lab, University of Technology Sydney, New South Wales, Australia
3Nu Instruments, Wrexham, UK
4School of Biomedical Engineering, University of Technology Sydney, New South Wales, Australia
5Graz Centre for Electron Microscopy, Graz, Austria
6Institute of Physics, University of Graz, Austria
7Department of Environmental Sciences, Informatics and Statistics, Ca’ Foscari University of Venice, Venice, Italy
8Gottfried Schatz Research Center, Medical Physics and of Biophysics, Medical University of Graz, Austria

Despite the natural ubiquity of nano- and microparticles and their increasing production and emission in anthropogenic processes, we struggle to understand their direct impact on the environment and health. This is anchored in their elusive nature and analytical challenges arising from it. Although current approaches can retrieve some facets, we are blind for a majority of properties or cannot retrieve them coherently. We are in a dire need to decipher basic traits of particles and gain more comprehensive insights in their compositions, size distributions and abundances. Only this way, we can advance on our understanding on origin, implication, and fate of particulate entities.

This presentation will showcase new strategies to enable a comprehensive molecular and elemental characterisation of single particles (SP). Through the on-line coupling of two-dimensional optical traps, SP Raman spectroscopy and SP ICP-TOFMS, it becomes possible to carry out non-target screenings, to decipher the molecular and elemental composition of individual entities as well as to determine number concentrations and size distributions. The presentation will detail the underlying considerations and strategies and focus on new instrumentation, its hyphenation and future potential.

References:

  1. C. Neuper, M. Šimić, T. E. Lockwood, R. Gonzalez de Vega, U. Hohenester, H. Fitzek, L. Schlatt, C. Hill, D. Clases. ChemRxiv, 2023.
  2. T. E. Lockwood, R. Gonzalez de Vega, Z. Du, L. Schlatt, X. Xu, D. Clases. J. Anal. At. Spectrom.,  2024, 39, 227-234.
  3. R. Gonzalez de Vega, T. E. Lockwood, L. Paton, L. Schlatt, D. Clases. J. Anal. At. Spectrom., 2023, 38, 2656-2663.

Hiram Castillo Michel

Hiram has a PhD in Environmental Science and Engineering from the University of Texas (2011) and more than 15 years of experience in the use of Synchrotron Radiation in Environmental and Life sciences. Since 2017, he has been a permanent scientist at beamline ID21 at, a beamline specialized in elemental bio-imaging and speciation using XRF microscopy and X-ray Absorption spectroscopy.

Hiram’s scientific activities involve using ID21 and other beamlines at ESRF to investigate the fate and transport of nanomaterials and potentially toxic elements at the tissue and cellular level in living organisms (microbes, plants, animal and human tissues) and other complex environmental samples. In the last 10 years, he has been involved in the development of sample preparation methods for biological samples, data analysis strategies and, recently leading the upgrade program of ID21 that will deliver a new microscope at ID21. 

Abstract

X-RAY MICROSPECTROSCOPY AT ESRF BEAMLINE ID21: METALLOMICS AT THE NANOSCALE

H. Castillo-Michel, M. Cotte, M. Salomé, G. Goulet, I. Fazlić, C. Hole

X-ray Nanoprobe, European Synchrotron Radiation Facility, Grenoble, France

Metallomics is an active research field, whether to understand metal biological roles, to improve food quality or to understand and prevent the accumulation of toxic metals in the food chains. This research domain is one of the core activities at beamline ID21 of the European Synchrotron. ID21 is a beamline dedicated to X-ray fluorescence (XRF) mapping and X-ray absorption spectroscopy (XAS) in the tender X-ray range (2-11keV), this energy range allows detecting important nutrient elements (P, S, K, Ca, Mn, Fe, Cu, Zn) as well as rare earths and pollutants (Cd, Ag, Ce, La, Gd). A brand-new X -ray nanoscope is being installed at the beamline to complement the existing microscope, and it will be soon available to users. It will offer enhanced capabilities for nano-XRF mapping, nano XAS and hyperspectral XRF mapping. This new state-of-the-art instrument will offer higher lateral resolution (down to 100 nm) with better XRF detection capacities (sub-ppm), higher acquisition speed, an improved cryogenic sample environment, preserving user-friendliness thanks to a new graphical user interface. Cryo-fixed biological samples can better cope with intense X-ray beams and the elemental distributions, chemical states, and sample morphologies are close to the in-vivo state under frozen-hydrated conditions. This presentation will highlight present and future capabilities at ID21 enabling metallomics at the nanoscale. Some examples of research done at ID21 will be used to illustrate sample preparation protocols, and data acquisition and analysis strategies.

Tasuku Hirayama

I received my Ph.D. in 2009 from Kyoto University under the guidance of Professor Yukio Yamamoto. Then, I joined the Christopher J. Chang group at University of California Berkeley as a JSPS postdoctoral fellow. After my postdoctoral work, I joined Gifu Pharmaceutical University as an assistant professor in Laboratory of Pharmaceutical and Medicinal Chemistry in 2010. In 2016, I was promoted to associate professor at the same laboratory. My research group has pioneered fluorescence probes for Fe(II) ion. My research interest is focused on the development of chemical tools to understand the metabolism of metal ions in living systems.

Abstract

DEVELOPMENT AND APPLICATIONS OF FLUORESCENT PROBES FOR LIVE IMAGING OF LABILE IRON AND LABILE HEME

T. Hirayama

Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu, Japan

Iron and heme are essential elements and biomolecules for living organisms and play central roles in biological functions, including oxygen transport and energy production. On the other hand, excess iron or heme causes cellular damage due to oxidative stress, and thus disruption of iron and heme homeostasis is involved in severe diseases, including cancer and neurodegenerative disorders. Currently, the dynamics of iron and heme in cells are still largely unresolved, and the development of tools to elucidate them is highly demanded. We have previously reported fluorescent probes that can selectively detect divalent iron, which is involved in intracellular iron transport and oxidative stress [1]. Recently, we succeeded in increasing the sensitivity of the divalent iron probe, set up a high-throughput screening system using it, and found new intracellular iron homeostasis-perturbed compounds [2]. On the other hand, the intracellular dynamics of heme is more unclear than that of iron, and it is necessary to develop a sensitive and highly selective method for its detection. We recently succeeded in creating a heme-selective fluorescent probe by optimizing the principle of the above divalent iron detection probe [3]. More recently, we have developed a method to detect heme not only in living cells but also in biological tissues, which enables us to visualize heme synthesis in the brain. In this presentation, we will introduce a series of probe developments and their applications.

References:

  1. T. Hirayama, K. Okuda, H. Nagasawa. Chem. Sci., 2013, 4, 1250-1256.
  2. T. Hirayama, M. Niwa, S. Hirosawa, H. Nagasawa. ACS Sens., 2020, 5, 2950-2958.
  3. K. Kawai, T. Hirayama, H. Imai, T. Murakami, M. Inden, I. Hozumi, H. Nagasawa. J. Am. Chem. Soc., 2022, 144, 3793.
Session: Public & Occupational Health

Joanna Collingwood

Joanna Collingwood is a Professor and Associate Head of Engineering at the University of Warwick in the UK, where she founded and leads the Trace Metals in Medicine Laboratory. Joanna holds degrees in Physics from York (MPhys) and Warwick (PhD). Her postdoctoral training was at Keele University (UK) and University of Florida (USA), where she held personal research fellowships from the Alzheimer’s Society, the Dunhill Medical Trust, EPSRC, and an Academic Research Fellowship from Research Councils UK.

She has a particular interest in the role of iron metabolism in brain disorders and has contributed to developments in synchrotron spectromicroscopy analysis of metals in human tissues, and in magnetic resonance imaging of iron levels in tissue samples, to inform clinical measurement of iron dysregulation in neurodegenerative disorders. Correlative imaging is increasingly a focus for her laboratory, including methods to enable label free microscopy of organic and inorganic tissue components. Joanna has served on numerous synchrotron facility user groups and panels at UK and European level, on the USA National High Magnetic Field Laboratory User Committee, and has served as Biomagnetics Editor for IEEE Transactions on Magnetics and on the UKSTFC and Alzheimer’s Society Biomedical Grant Advisory Boards

Abstract

NON-DESTRUCTIVE CHARACTERISATION OF TRACE ELEMENTS IN THE HUMAN BRAIN

J. Collingwood

School of Engineering, University of Warwick, Coventry, UK

Many trace metal elements are integral to life, yet aspects of their known form and function as biometals are unresolved, and many more are likely to be discovered. Analysis of trace metal elements in biological tissues presents a myriad of analytical challenges. Synchrotron x-ray spectromicroscopy offers new ways to overcome some of these challenges, and one area in which spectromicroscopy is being advanced and applied is the investigation of the role of metal elements in neurodegenerative disorders. Altered patterns of metal element distributions in tissues offer scope to improve diagnosis. Meanwhile, disease-associated changes in metal element utilization offer insights into neuropathology, and even scope for treatment.

Our motivation to advance analytical capabilities in this field is to better understand the role of metals in disease at regional, cellular, and subcellular levels, both to identify patterns of change that could be detected with clinical imaging methods and to inform the impact of metal-modifying drug treatments.

In order to advance our understanding of the role of trace elements, it is helpful to be able to determine non-destructively the distribution of trace elements as they relate to metabolites, proteins, cells, and tissues, the chemical state and local environment of each element, and their relationship with other chemical elements.

Most recently, we have sought to identify signatures in synchrotron x-ray spectra to enable mapping of organic tissue components of interest, so that these can be directly correlated with metal element distributions and their chemical properties. Examples that will be used to illustrate this approach include i) the label-free observation of neuromelanin in tandem with iron as determined by scanning transmission x-ray microscopy, and ii) the discovery of evidence for iron and copper in metallic form in protein deposits from the brains of individuals who had Alzheimer’s disease.

Synchrotron light sources provide access to intense focussed beams of x-rays, providing an outstanding tool for multi-modal non-destructive analysis of iron with outstanding analytic sensitivity and specificity. Burgeoning interest, coupled with technical advances and beamline development at synchrotron facilities, has led to substantial improvements in resources and methodologies in the field in recent years.

Juergen Gailer

Dr. Gailer completed his PhD at the University of Graz in Austria back in 1997. As an Erwin Schroedinger fellow, he then moved to the Department of Molecular and Cellular Biology at the University of Arizona in Tucson, USA. Soon after, he transferred to the Department of Nutritional Sciences as a research associate. He relocated to the GSF National Research Center for Environment and Health in Munich, Germany in 2001, where he stayed until 2002 as an Alexander von Humboldt fellow. In 2003, he started working as a team leader in biopharmaceutical production at Boehringer Ingelheim in Vienna, Austria. He then joined the Department of Chemistry at the University of Calgary in 2004, where he is currently a Full Professor. His research focusses on developing and applying instrumental analytical chemistry approaches to bioinorganic chemistry-related problems related to toxicology and the advancement of more anticancer active metal-based drug candidates to clinical studies.

Abstract

TRANSLATIONAL TOXICOLOGY: LINKING TOXIC METAL(LOID) SPECIES TRAFFICKING IN THE BLOODSTREAM-ORGAN SYSTEM TO ADVERSE HUMAN HEALTH EFFECTS

J. Gailer, M. Doroudian, N. Pourzadi

Department of Chemistry, University of Calgary, Calgary, Canada

In 2015 9 million premature deaths globally were attributed to the exposure of human populations to natural and increasingly man-made chemicals that are present in air, food and water resources. Pollution thus represents an enormous public health problem which – since it also affects reproductive health – has effectively become a planetary threat. In terms of pollutant classes that need to be considered, arsenic, mercury, cadmium and lead are in a league of their own as they cannot be degraded and therefore tend to accumulate in ecosystems.

Linking chronic human exposure to the aforementioned metal(loid) species to adverse health effects, however, is exceedingly difficult. While their quantification in the human bloodstream is routinely used to assess exposure to these potentially toxic metal(loid) species, the interpretation of the obtained data in terms of their cumulative health relevance remains problematic. Seemingly unrelated to this, epidemiological studies strongly suggest that the simultaneous chronic exposure to these inorganic pollutant species is associated with the etiology of autism, type 2 diabetes, irritable bowel disease and possibly other diseases. From a public health point of view this undesirable situation urgently requires us to establish functional connections between human exposure to multiple toxic metal(loid) species and adverse health effects. One way to establish causal exposure-response relationships is a bioinorganic chemistry or molecular toxicology approach, which requires one to unravel the biomolecular mechanisms that unfold after individual toxic metal(loid) species enter the bloodstream/organ nexus as these interactions ultimately determine which metabolites impinge on target organs and thus provide mechanistic links to diseases of unknown etiology. To underscore the importance of the toxicological chemistry of metal(loid) species in the bloodstream, this presentation will highlight bioinorganic processes that are implicated in the etiology of adverse organ-based health effects and possibly diseases. The integration of these processes into the biological organism will not only help to advance the regulatory framework to better protect humans from the adverse effects of multiple toxic metal(loid) species, but also represents a starting point for the development of treatments to ameliorate pollution-induced adverse health effects in human populations, including pregnant women, the fetus and children.

Session: Metal Ecotoxicology, Homeostasis & Bioremediation

Liz Rylott

Liz Rylott is an Associate Professor at the Centre for Novel Agricultural Product (CNAP), in the Department of Biology at the University of York, UK. She received her Ph.D. in Plant Genetics and Biochemistry from The John Innes Centre, University of East Anglia, Norwich, UK.

A long-standing member, and current Executive Vice-President, of the International Phytotechnologies Society, and keen plant botanist, Liz is interested in how plants and biotechnology can be harnessed to remediate pollution and recover technology-critical elements from our environment. Her group studies a range of environmental pollutants including precious and platinum group metals, rare earth elements, explosives and halogenated aliphatic compounds. Her research is focused on understanding the genetic mechanisms involved in the stress responses and detoxification of these xenobiotics in plants.

Dr Rylott has been involved in key achievements including the first demonstration of a biochemical system to degrade the explosive compound RDX, and subsequent characterisation of a structurally-unique cytochrome P450; engineering a complete in planta catabolic pathway for the degradation of 1,2-dichloroethane; elucidating the mechanism of TNT phytotoxicity and downstream detoxification pathways; and the first field-trial to demonstrate the efficacy of genetically modified plants to remediate organic pollution (RDX).

Abstract

USING PLANTS TO REMEDIATE METAL-POLLUTED ENVIRONMENTS AND RECOVER TECHNOLOGY-CRITICAL ELEMENTS

E. Rylott1, R. McElroy2



1Department of Biology, University of York, York, UK
2School of Chemistry, University of Lincoln, Lincoln, UK

Human activities, such as mining, have discharged significant quantities of metals and metalloids into our environment, posing acute risks to human health. Additionally, reserves of technology-critical metals are depleting rapidly. Phytoremediation and phytomining offer potential, nature-based solutions to restore polluted environments and recover these valuable elements.

To establish if plants can grow on metal-rich waste sources such as mine tailings, identify bottlenecks to the solubilisation, uptake and detoxification of these elements by plants and associated bacterial communities; develop down-stream processes to valorise the harvested biomass, and recover the metals.

A range of plant species and cultivars, including willow (Salix sp.), Phytolacca america (pokeweed), and model molecular biology species Arabidopsis thaliana, were grown in waste media, artificially dosed soil, or hydroponic systems containing nickel, gold, palladium tailings or rare earth elements. Metal uptake was monitored using ICP-OES (Inductively coupled plasma – optical emission spectrometry) and ICP-mass spectrometry (ICP-MS). The effect of bioaugmentation with Plant Growth Promoting, and cyanogenic, bacterial consortia was monitored, and transcriptomics expression studies conducted.

We identified specific plant species and cultivars with relatively high metal uptake and tolerance indices. Co-cropping, and/or bioaugmentation with cyanogenic plant and bacterial species increased metal uptake, but at the expense of plant biomass production. Gene expression studies on these plants led to the identification of key metal transporter and chelators target genes. Following microwave pyrolysis of the nickel-rich biomass, we were able to demonstrate that biologically bound Ni increased the catalytic hydrogenation of cinnamaldehyde, and de-polymerisation of the plastics polyethylene and polystyrene.
The results demonstrate that plants can grow on metal-rich waste sources, but that metal solubilisation, uptake and detoxification are key barriers to the success of this technology. Further studies are needed to develop biomass crop species tailored to hyperaccumulate specific metals.

Cecilia Martinez-Gomez

Abstract

UNRAVELING LANTHANIDE-DEPENDENT METHYLOTROPHY TO DEVELOP PLATFORMS TO RECOVER LANTHANIDES FROM COMPLEX WASTE SOURCES

C. Martinez-Gomez

Plant and Microbial Biology, University of California, Berkeley, United States of America

Lanthanide metals, long appreciated for their essential roles in technology, have recently been identified as critical elements for biology. Like other life metals, they are found in poorly soluble sources in nature, yet are widely used as cofactors for alcohol dehydrogenases involved in methylotrophy and one-carbon metabolism. My laboratory is studying how methylotrophs can sense, transport, use, and store lanthanides. We have identified a novel lanthanide chelator that we named methylolanthanin that is secreted to sequester lanthanides by the methylotroph Methylobacterium extorquens AM1 using transcriptomics, bioinformatics, and mass spectrometry analysis. In addition, we have identified a lanthanide transport system, novel trafficking enzymes, and new classes of enzymes that use lanthanides. My laboratory has also expanded the role of lanthanides to multi-carbon metabolism with substrates such as sugars and aromatic acids in organisms other than M. extorquens AM1, and we are currently identifying the metabolic involvement of these metals in diverse pathways. In addition, we are engineering methylotrophs to efficiently recover lanthanides from waste sources.

Session: Health & Disease

Michael Aschner

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. Research in our lab focuses on the following topics:
(1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of methylmercury (MeHg)uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure.

(2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2function increase MeHg’s neurotoxicity.

(3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress.
Our studies are designed to, (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Abstract

SLC30A10 IS A CELL SURFACE-LOCALIZED MANGANESE EFFLUX TRANSPORTER, AND MUTATIONS ASSOCIATED WITH PARKINSONISM BLOCK ITS INTRACELLULAR TRAFFICKING AND EFFLUX ACTIVITY

M. Aschner

Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, USA

Homozygous mutations in SLC30A10 cause familial parkinsonism associated with manganese (Mn) retention. We recently identified SLC30A10 to be a cell surface-localized Mn efflux transporter and demonstrated that parkinsonism-causing mutations block its intracellular trafficking and efflux function. In C. elegans, SLC30A10 over-expression protected against Mn-induced lethality and dopaminergic neurotoxicity, consistent with results in mammalian systems. Here, we present new data about SLC30A10 function in C. elegans. SLC30A10 expression did not protect worms against ZnSO4toxicity, suggesting that SLC30A10 does not mediate Zn export in C. elegans. Furthermore, while a blast search identified 5 potential SLC30A10 homologs in worms (cdf-1, cdf-2, ttm-1 and toc-1; sequence identity <35%), knock-down of these genes showed a tendency of increased survival after Mn exposure (although only ttm-1 was statistically significant), suggesting that the worm homologs may function differently.

Tolunay Beker Aydemir

Tolunay Beker Aydemir, Ph.D.,is an Assistant Professor of Molecular Nutrition at Cornell University Division of Nutritional Sciences. She obtained her Ph.D. in Biomedical Sciences with a concentration in Biochemistry and Molecular Biology at the University of Florida College of Medicine. She completed her postdoctoral studies in the Nutritional Genomics Laboratory, Center for Nutritional Sciences at the University of Florida.

Dr. Aydemir’s research is dedicated to understanding the regulation of various cellular processes by zinc and manganese, which are essential for maintaining good health. Specifically, she investigates the role of the Solute Carrier (SLC) family of metal transporters in mediating the tissue-, organ-, and cell-specific functions of these trace minerals. Her interdisciplinary approach to research, which employs biochemistry, molecular biology, and nutritional genomics methods, provides a comprehensive understanding of zinc dynamics by integrating tissue studies, cellular immunity, and genetic approaches. Dr. Aydemir’s research is at the forefront of the examination of trace-mineral function, offering a nuanced understanding and enabling the discernment of therapeutic roles for transition metals.

Abstract

ZINC IN DYNAMIC REGULATION BETWEEN GUT MICROBIOME AND HOST METABOLISM

T. Beker Aydemir

Division of Nutritional Sciences, Cornell University, Ithaca, USA

Dietary metals have been shown to be involved in the regulation of gut microbial diversity and composition. However, studies linking the action of gastrointestinal metal transporters to gut microbial regulation are lacking.

To investigate the associations between disease signatures and changes in zinc (Zn) transporters, Zn homeostasis, and gut microbiome in gastrointestinal disorders, including inflammatory bowel disease (IBD). The specific focus was to determine the impact of the host metal transporter gene Slc39a14/Zip14 deletion on the composition of the gut microbiome and to understand how ZIP14-linked changes in the gut microbiome and serum metabolome could affect host metabolism.

The preclinical IBD models were chemically induced by dextran sulfate salt (DSS) and interleukin 10 (IL-10) knockout (KO) (genetically engineered). Our genetically modified in-house mouse models were whole-body Zip14 KO and intestine-specific Zip14 KO. Microwave plasma atomic emission spectrometry was used to measure Zn concentrations. Zinc transport studies were conducted using 65Zn. Permeability assays were with FITC-dextran (FITC-dextran 4). Shotgun metagenome sequencing was conducted to look for differential abundances of taxa between the microbial communities of Zip14 KO and wild-type mice. Serum untargeted metabolomics profiling was done using gas chromatography (GC) coupled to time-of-flight mass spectrometry (TOF-MS).

We found that ZIP14 was downregulated in human colon biopsies from patients with IBD and in preclinical models of IBD. Deletion of Slc39a14/Zip14 caused Zn deficiency in the entire intestinal tract, leading to a shift in gut microbial composition that partially overlapped with changes previously associated with obesity and IBD, increased the fungi/bacteria ratio in the gut microbiome, altered the host metabolome, and shifted host energy metabolism toward glucose utilization.

Our results suggest a potential pre-disease microbial susceptibility state dependent on host gene Slc39a14/Zip14 that contributes to intestinal permeability, a common trait of IBD, and metabolic disorders such as obesity and type 2 diabetes.
Our findings provided new insight into understanding host metal transporter gene-microbiome interactions in developing chronic disease by providing evidence linking the mammalian metal transporter ZIP14 to gut microbiome composition, host serum metabolome composition, and energy metabolism changes.

Rachel Codd

Rachel Codd is the Professor of Bioinorganic and Medicinal Chemistry at The University of Sydney and leads the Chemical Biology in Drug Discovery group in the School of Medical Sciences. Her research blends the use of organic and inorganic chemistry, and molecular and chemical biology to engineer metal-coordinating bacterial secondary metabolites and analogues as new chelators with broader function across the realms of radiopharmaceuticals, antibiotics, anticancer agents, and metal detoxification. The quest for molecular discovery in her group is underpinned by a strong cross-discipline approach and interests in technology development. After completing her PhD in Inorganic Chemistry at The University of Sydney, she undertook postdoctoral research at the University of NSW and the University of Arizona before returning to The University of Sydney.

Rachel was awarded the Biota Medal in 2010, sat on the Australian Research Council (ARC) College of Experts (2016–2018), and was elected as a Fellow of the Royal Australian Chemical Institute (RACI) in2017. She is a member of the Editorial Advisory Boards of the Journal of Inorganic Biochemistry and the Journal of Biological Inorganic Chemistry. She enjoys working with her team of Honours and PhD students and postdoctoral research associates, and academic colleagues and collaborators.

Abstract

Developing siderophore-inspired platforms for drug discovery

R. Codd

School of Medical Sciences, University of Sydney, Sydney, Australia

Siderophores are low-molecular-weight Fe(III) binding chelators produced by bacteria [1]. This class of natural product chelator provides a rich foundation for integrating chemical microbiology, chemical biology, and bioinorganic chemistry approaches to bioengineer new analogues and develop siderophore-based technology platforms to support drug discovery.

Siderophores play key roles in bacterial iron supply, which identifies opportunities to use analogues in antibiotic discovery as pathway disruptors or as drug-import vectors. The metal-binding pharmacophore of siderophores has broader drug discovery potential in the discovery and/or disruption of disease-relevant metalloproteins in cancer and cardiovascular disease.

Our quest to advance methods to diversify the structure and function of siderophores has focused on the clinical hydroxamic acid-containing siderophore desferrioxamine B (DFOB). We have used precursor-directed biosynthesis to produce libraries of DFOB analogues with (bio)isosteric replacements along the methylene backbone with potential in antibiotic delivery, bio-surveillance, and metallo-radiopharmaceutical development [2, 3]. We have modified DFOB to produce chemical probes for target discovery [4, 5] and other drug-like fragments [6], and developed new methods founded on the principles of bioinorganic chemistry with broader applicability in metal-inspired drug discovery [7].

This paper will showcase the untapped potential of siderophores and other natural product chelators in technology development and medicinal chemistry research.

References:

  1. R. C. Hider, X. Kong. Nat. Prod. Rep., 2010, 27, 637–657.
    M. Sandy, A. Butler. Chem. Rev., 2009, 109, 4580–4595.
    R. Codd, Comprehensive Inorganic Chemistry III, 2023, 2, 3–29.
  2. T. Richardson-Sanchez, R. Codd. Chem. Commun., 2018, 54, 9813–9816.
  3. T. Richardson-Sanchez, W. Tieu, M. P. Gotsbacher, T. J. Telfer, R. Codd. Org. Biomol. Chem., 2017, 15, 5719–5730.
  4. M. P. Gotsbacher, R. Codd. ChemBioChem, 2020, 21, 1433–1455.
  5. J. Ni, J. L. Wood, M. Y. White, N. Lihi, T. E. Markham, J. Wang, P. T. Chivers, R. Codd. RSC Chem. Biol., 2023, 4, 1064–1072.
  6. T. Richardson-Sanchez, W. Tieu, R. Codd. ChemBioChem, 2017, 18, 368–373.
  7. L. Roth, M. P. Gotsbacher, R. Codd. J. Med. Chem., 2020, 63, 12116–12127.
Session: Biogeochemical Cycles

Robert Newton

Robert (Bob) Newton is an oceanographer specializing in atmosphere/ice/ocean interactions in the Arctic and its peripheral seas. He also works with noble gases, stable isotopes, nutrients, and other trace chemical signals to derive provenance and pathways of water masses in ocean. Bob founded and directed the Secondary School Field Research Program (SSFRP), Lamont-Doherty’s internship program for pre-University students. The SSFRP recruits mainly from communities underrepresented/underserved in earth and environmental science; it is the most diverse of Lamont-Doherty’s educational programs. The program centres field- and lab-based research related to the Hudson estuary, New York Harbor, and green spaces in the NYC metropolitan area. Bob has retired from Lamont, but still teaches in the Sustainability Science master’s program. 

Abstract

MASS FLOWS, GEOTRACES AND MARINE METALLOMICS

R. Newton



Lamont-Doherty Earth Observatory, Columbia University, New York City, USA

I’ll discuss two socio-technical developments that are important to the study of marine metallomics. The first is the GEOTRACES program, which represents a leap forward in observational capacity, both through its measurement technologies and its organizational dynamics. Over the past decade, we have surveyed the world ocean for metals and metalloids at detection limits that are commensurate with the concentrations of metals in cells and the gradients between their ecological niches. As a result, we can begin to differentiate between marine metallomes and to ask questions about the relationship between those metallomes and their supported ecologies. Secondly, we will review the massive shift in relative contributions of human and non-human processes in setting the fluxes of metals and other materials to the world ocean. When the speaker was born, less than 20% of the material set in motion on Earth’s surface was taken into the human economy. In 70 years that ratio has approximately reversed. One has to wonder what the implications are for marine and lacustrine metallomes.

For 20 years, Lamont’s geochemistry division has hosted a large mentorship program, which the speaker directed, engaging students from groups under-represented in our fields. I will discuss how we integrated young investigators into research projects. If you are interested in using internships and outreach programming to address longstanding biases in our institutions, please reach out and we can make time to talk).

References:

  1. R. C. Hider, X. Kong. Nat. Prod. Rep., 2010, 27, 637–657.
    M. Sandy, A. Butler. Chem. Rev., 2009, 109, 4580–4595.
    R. Codd, Comprehensive Inorganic Chemistry III, 2023, 2, 3–29.
  2. T. Richardson-Sanchez, R. Codd. Chem. Commun., 2018, 54, 9813–9816.
  3. T. Richardson-Sanchez, W. Tieu, M. P. Gotsbacher, T. J. Telfer, R. Codd. Org. Biomol. Chem., 2017, 15, 5719–5730.
  4. M. P. Gotsbacher, R. Codd. ChemBioChem, 2020, 21, 1433–1455.
  5. J. Ni, J. L. Wood, M. Y. White, N. Lihi, T. E. Markham, J. Wang, P. T. Chivers, R. Codd. RSC Chem. Biol., 2023, 4, 1064–1072.
  6. T. Richardson-Sanchez, W. Tieu, R. Codd. ChemBioChem, 2017, 18, 368–373.
  7. L. Roth, M. P. Gotsbacher, R. Codd. J. Med. Chem., 2020, 63, 12116–12127.

Dr. Jörg Rinklebe

Dr. Jörg Rinklebe is Full Professor for Soil- and Groundwater-Management at the University of Wuppertal, Germany. He was Highly Cited Researcher in 2019, 2020, 2021, 2022. Prof. Rinklebe is now Past President of the International Society of Trace Element Biogeochemistry (ISTEB). His academic background covers environmental science, bioavailability of emerging contaminants, and remediation of contaminated sites. His main research is on soils, sediments, waters, plants, and their pollutions and linked biogeochemical issues with a special focus in redox chemistry. Prof. Rinklebe published 510 scientific papers in leading international and national journals (h-index = 89). Also, he published four books as well as numerous book chapters. He is serving as Editor in Chief for Environmental Pollution. He was the chair of the first joint international conferences of Biogeochemistry of Trace Elements” (ICOBTE) and “International Conference on Heavy Metals in the Environment” (ICHMET) in September 2023. He was an invited speaker (plenary and keynote) at many international conferences. He is Honorable Ambassador for Gangwon Province, South-Korea, Adjunct Professor at the University of Southern Queensland, Australia, Visiting Professor at the Sejong University, Seoul, South Korea and Guest Professor at the China Jiliang University, Hangzhou, China.

Abstract

Biogeochemical cycling of arsenic in soil and water around the globe

Jörg Rinklebe

Faculty of Architecture und Civil Engineering
University of Wuppertal

Arsenic is a ubiquitous hazardous metalloid that can threaten ecosystem and human health through bio-accumulation and bio-magnification in the food chain. Arsenic has been considered as a proverbial carcinogen, which may cause several diseases such as cardiovascular disease, infertility, diabetes, neurological problems and skin lesions. This is highly problematic since many soils and waters and food around the globe are contaminated with As. This contamination is caused by geogenic sources such as weathering processes, geochemical reactions and biological activities as well as anthropogenic activities, including mining and smelting industries, agricultural applications, sewage irrigations, and fossil fuel combustions and other industrial activities.

During the last two decades substantial progress have been made concerning the elucidation of the processes which govern the mobilization and immobilization of arsenic in the soil water interface. However, this knowledge is still incomplete and always need to be modified to site specific conditions around the globe. The interactions are complex since numerous factors such as redox potential, pH, iron, phosphate and others are involved into those processes. Within this context, it is of great importance to develop mitigation strategies and cost-effective technologies to remediate As-contaminated soils and waters. The presentation will provide an overview over numerous laboratory and field studies from a global perspective.

References:

  1. R. C. Hider, X. Kong. Nat. Prod. Rep., 2010, 27, 637–657.
    M. Sandy, A. Butler. Chem. Rev., 2009, 109, 4580–4595.
    R. Codd, Comprehensive Inorganic Chemistry III, 2023, 2, 3–29.
  2. T. Richardson-Sanchez, R. Codd. Chem. Commun., 2018, 54, 9813–9816.
  3. T. Richardson-Sanchez, W. Tieu, M. P. Gotsbacher, T. J. Telfer, R. Codd. Org. Biomol. Chem., 2017, 15, 5719–5730.
  4. M. P. Gotsbacher, R. Codd. ChemBioChem, 2020, 21, 1433–1455.
  5. J. Ni, J. L. Wood, M. Y. White, N. Lihi, T. E. Markham, J. Wang, P. T. Chivers, R. Codd. RSC Chem. Biol., 2023, 4, 1064–1072.
  6. T. Richardson-Sanchez, W. Tieu, R. Codd. ChemBioChem, 2017, 18, 368–373.
  7. L. Roth, M. P. Gotsbacher, R. Codd. J. Med. Chem., 2020, 63, 12116–12127.

ISM9 offers early bird, standard, and on-site registration fees for regular participants and students both in person and virtual.

Interested in early bird alerts?