MNDA Dublin 2016 – Reflections on Day 1

The Dublin Convention Centre on the north bank of the Liffey seems a nice setting for the 27th International MNDA conference.  It looks very modern with its unusual “sloping cylinder” glass frontage and the atrium with its zig-zagging escalators is certainly a grand space to behold.  It was fun to hear from former Irish President Mary Robinson, who came to speak to us to open the meeting.  Apparently she is now Chancellor of Trinity College Dublin.

After hearing from Mrs Robinson, we were treated to an exposition of the “exposome” and its contribution to ALS by Roel Vermeulen (Utrecht).  Environmental factors are notoriously difficult to measure and so it is of interest to hear that we can now start to use big data approaches in conjunction with ‘omics technologies to address the contribution of environmental exposures.  “Your genes load the gun and your environment pulls the trigger” was one memorable quote.  What is clear is that our environment does indeed leave epigenetic signatures in our bodies, which can evolve over time depending on whether that exposure is curtailed or continued.  Actually it reminds me somehow of a BBC News item I read a couple of weeks ago about how it’s now possible to determine parts of a person’s health status from the traces of biological residue their fingertips leave on their smartphone screen!  Could you call that the “phoneome”?  E.T. phoneome! 🙂  Well, my own personal opinion is that the transient and highly dynamic nature of epigenetics, while pesky for researchers to study, is really a beacon of hope in the otherwise all-too-dark sea of despair that is inherited disease.  For if your environment can pull the trigger then it can also hopefully be persuaded (with the correct molecular counselling) to put the gun down!

The second plenary was an episode of the X-files (ALS-style starring Richard Bedlack from Durham NC, USA).  It’s all too easy to be lured into using unproven and untested alternative treatments when confronted by sensationalist claims and miraculous anecdotes.  And yet, could there be threads of gold in amongst the gold-coloured hay?  A small number of patients with apparently clinically robust diagnoses of ALS look to have made seemingly inexplicable recoveries.  Do such patients hold important biological clues to understanding and treating this disease?  It is not beyond biological plausibility to think there may be some individuals who are resistant to the ALS disease process.  The story of CCR5 mutations in patients resistant to HIV has shown us that such serendipitous discoveries can be made and so, as long as the pathogenesis of ALS remains a largely opaque picture, I think we would be foolish not to follow up on these possibilities.

After lunch there was a focus on RNA biology and protein misfolding.  Looking at the programme, there was less directly about C9orf72 than there has been at previous meetings.  I’m not sure why that’s the case.  Perhaps for now the relatively quick and easy “low-hanging fruit” studies on C9orf72 are thought to have been already picked!  However, I expect next time there will be more about it once again.  There were some very good talks in these sessions about the spread of mutant misfolded proteins in ALS.  However, the most memorable talks for me were about worms and fish.  C. elegans is truly a great model organism, as shown by Alex Parker (Montreal).  It has 1000 cells and just 302 neurons.  Its genome shares many genes (35%?) with humans and it has great high-throughput potential, not only for disease modelling but also for drug screening.  Similarly, zebrafish share 75% genes with humans and have the benefit of being see-through in their larval stages (which I gather do not legally count as fish up until 5 days or so).  Some spectacular live imaging of zebrafish spinal cord neurons and glia was shown by Marco Morsch (Macquarie University, Sydney).  Using clever labelling, UV laser confocal microscopy can be used to selectively kill individual neurons.  A microglia then comes along and cleans up the mess.  Other microglia also investigate but move on once they realise another microglia is already sorting it out.  I guess maybe microglia have feelings too!

Thanks for an interesting first day – roll on day 2!