The annual MND Australia Research Meeting for 2014 was held at The Florey Institute, University of Melbourne 27th November. There was an air of excitement at the meeting due to the recent world wide phenomenon that was ice bucket challenge, which has not only raised vital funds to allow much needed research in to the causes of MND but has also significantly raised the profile of MND in the Australian community. Fittingly, on this particular Monday morning Melbourne decided to open its skies and hold its own version of the ice bucket challenge with huge thunderstorms crashing across the city resulting in train and tram line failure and more than a few meeting attendees arriving soaking wet.
The meeting was bigger and better than ever with 21 platform presentations, 27 posters and over 100 people registered to attend. The meeting was opened with the announcement that the MND Australia Research Committee Chair Professor Dominic Rowe AM had stepped down. Prof Rowe, of Macquarie University, has lead the MND research committee since he took over the role at the end of 2004. During those ten years Prof. Rowe has spearheaded enormous change and exponential growth of MND research in Australia. He has overseen the introduction of funding for PhD scholarships, top-up grants, annual awards of early career postdoctoral fellowships, a major four-year grant for mid career MND researchers and, thanks to the MND Ice Bucket Challenge, a major project grant for an MND research team will be awarded in 2015. On stepping down after ten years, Dom leaves MNDRIA in a very strong position providing greater than $2.5 million for MND research for 2015. The position of MND Research Committee Chair has been taken up by Prof Matthew Keirnan, NeuRA UNSW, who certainly has some big shoes to fill.
Prof Phil Beart, head of neurodegeneration at the Florey Institute gave the opening address and kicked the day off by speaking about protein misfolding and aggregation and the need to “take out the trash” using protein degradation machinery. His insights into neuron specific processes set the tone. On the subject of protein misfolding Prof Ken Rodgers, University Technology Sydney provided evidence that the blue green algae toxin BMAA can be misincorporated in to growing polypeptides which may cause protein misfolding and aggregation. It was proposed that non-proteinogenic amino acids such as BMAA may accumulate in misfolded proteins throughout life and result in MND. One way of degrading such misfolded proteins is autophagy and Dr Brad Turner of the Flory Institute, University of Melbourne, presented his work outlining small molecule activation of autophagy and its consequences on accumulation of misfolded and aggregated proteins. It seems the effectiveness will depend on which specific autophagy pathway is targeted.
While there have been many recent discoveries outlining genetic causes of MND there is still a significant amount of inherited forms of MND in which a genetic defect is not identified. As a result, genetics of MND is still a hot topic and Prof. Ian Blair, and Dr Kelly Williams from Macquarie University spoke on the use of next generation sequencing and epigenetics in the study of MND respectively. In addition, Beben Benyamin from the University of Queensland spoke about his work on genomic and epigenetic changes in the Chinese population. Studying specific populations seems important due to the differences in inheritance such as the lower age of onset in the Chinese population compared to the European population and the lower frequency of c9orf72 expansions. It appears that as we move forward with genetic studies we may have to move towards studying polygenic analysis of common SNPs. Importantly, we were reminded that the discoveries made in the genetics arena feed in to the study of molecular and cellular biology and provide more pieces to the puzzle. This lead directly to the construction of model systems to study these genetic discoveries such as the zebra fish presented by Dr Nick Cole, Macquarie University, and the iPSC derived motor neurons generated in the laboratory of Dr Lezanne Ooi, University of Wollongong. Importantly, Dr Ooi’s models were generated with mRNA so as not to change the DNA of the patient cells and the models recapitulated major MND phenotypes such as increases in phosphorylated TDP-43.
Prof Peter Noakes, University of Queensland, advocated for the use of human tissue in the study of MND and showed some breathtaking images of neuromuscular junctions from human muscle biopsy. ALS NMJs were significantly fragmented, withdrawn, and showed terminal sprouting. Dr Catherine Blizzard, University of Tasmania, presented work to suggest that TDP-43 plays an important role in the maintenance of the synapse through delivery of vital mRNA. While the cytoskeleton, was shown to be important to trafficking of TDP-43 in to axons by the work of Dr Anna King also of the University of Tasmania.
Cellular signaling also was a prominent theme in the presentations with Dr Marie Mangelsdorf, University of Queensland, presenting her work on the EphA4 protein, its splice variants and its role in speed of disease progression. Further, Dr Jeff Liddell presented work to show that the copper containing drug used in his laboratory at the University of Melbourne activated the Nrf2 pathway possibly leading to beneficial effects. Lastly, Dr Aaron Russell, Deakin University, presented his work showing that mitochondrial health and thus motor neuron survival may be promoted by suppressing specific micro RNA that control mitochondrial gene expression.
The poster session followed and was a hive of activity, with many discussions around the interesting work being presented. By then the clouds had parted and we could all make our way home and reflect on how fast the field is growing, what the year 2014 has delivered and what major challenges lie ahead.