SEGH Articles

# Winner of the Malcolm Brown Outstanding Young Scientist Award

12 August 2016
Gabriel Enge won the Malcolm Brown outstanding young scientist award at the 32nd SEGH International conference in Brussels. He describes his research leading to this award.

I am a research scientist, working on the application of medical isotope metallomics to neurodegenerative diseases. Neurodegenerative diseases are characterized by a progressive loss of neuron function. Illnesses, such as Parkinson’s, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) are located within the family of neurodegenerative diseases.

Amyotrophic lateral sclerosis was first described in 1869 (Charcot & Joffroy 1869) and is a fatal, predominantly adult-onset neurodegenerative disease that leads to the selective death of motor neurons (Redler & Dokholyan 2012; Rowland & Shneider 2001). This selective death causes progressive muscle paralysis and spasticity, affecting mobility, speech and respiration (Hardiman et al. 2011). Most patients are fully aware of the disease progression, with about half of all affected individuals passing away within 3-5 years of diagnosis, while less than 20% survive more than 5 years (Robberecht & Philips 2013). Approximately 90% of ALS cases are sporadic, and the remaining, familial (Robberecht & Philips 2013). The neuropathology of ALS is staggeringly complex on a subcellular level and includes abnormalities in almost every cellular compartment. It was additionally observed that concentrations of several elements were elevated in the cerebro spinal fluid of ALS patients (Roos et al. 2013), and that mouse models demonstrated specific accumulations of metals (Cu, Zn) in key tissues, such as brain and spinal cord (Li et al. 2006; Tokuda et al. 2007; Tokuda et al. 2013). In spite of our tremendous advances into understanding the disease and its progression in the past 150 years, no diagnostic tools or cures are currently available.

Here at the University of Wollongong, in the Wollongong Isotope Geochronology Laboratory, I have established with my PhD project a new way of looking at the disease. By taking a mouse model of the disease, and applying geochemical analytical techniques of measuring metal concentrations and Cu isotope ratios in tissues, I attempt to gain a more profound understanding of metabolic perturbations that involve metals, in particular Cu. One of the novelty factors of the research includes a time and disease development dependent resolution of changes in metal concentrations and Cu isotope ratios. Future work includes a spatial resolution component using laser ablation methods.

Besides my interest in neurodegenerative diseases, I am also very interested in using metallomics and isotope methods to trace ageing processes in humans, and explore different metabolic ageing processes. Another interest is the continued automation of manual ion-exchange chromatography procedures in order to be able to establish them as part of clinically-diagnostic routines.

Heading: Fun at work with the Neptune Plus MC-ICP-MS

"Let's keep looking in spite of everything. Let us keep searching. It is indeed the best method of finding, and perhaps thanks to our efforts, the verdict we will give such a patient tomorrow will not be the same we must give this man today" - Jean-Martin Charcot (1889).

Charcot's words have been my inspiration since the start of my candidacy and I want to express my deep gratitude for receiving the Malcolm Brown Outstanding Young Scientist Award. I realise that I am not at a stage of my career where I have much to show yet, and therefore I am especially thankful for this indication of support from the community.

By T. Gabriel Enge, PhD Candidate, School of Earth and Environmental Sciences, University of Wollongong, Australia

References

J. Charcot and A. Joffrey, Arch. Physiol. Norm. Pathol., 1869, 2, 354-744.

R.L. Redler and N.V. Dokholyan, Prog. Mol. Biol. Trans. Sci., 2012, 107, 215-262

L.P. Rowland and N.A. Schneider, N. Engl. J. Med., 2001, 344, 1688-1700.

O. Hardiman et al., Nat. Rev. Neurol., 2011, 7, 639-649.

W. Robberecht and T. Philips, Nat. Rev. Neurosci., 2013, 14, 248-264.

P.M. Roos et al. Biol. Trace Elem. Res., 2013, 151, 159-170.

Q-X Li et al. Aging Cell, 2006, 5, 153-165.

E. Tokuda et al. Toxicology, 2007, 229, 33-41.

E. Tokuda et al., Neurobiol. Dis., 2013, 54, 308-319.

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