“Welcome to this afternoon’s genetics session, which I hope will convey elements of hope and excitement about the season of the gene” were Professor Teepu Siddique’s (from Northwestern University, USA) opening remarks on a series of talks that really did live up to this standard. To me each talk was like being read chapters of a thriller novel, each was gripping with its own story to tell, but by the end of the session I was really buoyed up with hope, enthusiasm and an appetite for more!
Prof Siddique’s research lab have contributed two important new discoveries in MND genetics in the last few months alone (UBQLN2 and SQSTM1), so he was very well placed to begin with an overview of how recent discoveries allow us to make sense of much of what has been to date.
Prof Siddique started his talk by discussing what we can tell about MND by looking at human motor neurones down a microscope . Using some very elegant studies of the build up and removal of proteins tagged with different colour labels he demonstrated that many causes of MND (ie genetic mistakes in TDP-43, SOD1 and FUS genes, and the randomly occuring sporadic form) all have a build up of ubiquilin2. The next part of the story was to explain what this protein was doing there – what sequence of events or malfunctions in the motor neurone has caused the protein to be there. Time and again he demonstrated that at the heart of disease-causing damage in MND is the protein recycling system (see Prof Mayer’s post a month or so ago). This was summed up for delegates by playing a TV commercial of blindfolded women trying to identify different parts of an animal (a rhino this time) and only when their blindfolds were removed was the whole story revealed.
The phrase an ‘elephant in the room’ is used in reference to the presence of a huge topic that no-one is talking about. But the huge topic in genetics was most definitely getting an airing this afternoon – that of the discovery of the C9orf72 gene defect. Speakers either talked about it in light of the way that it links together a number of diseases where there is evidence of frontotemporal dementia as well as signs of motor neurone damage. Or the fact that the actual gene defect seen in C9orf72 is so different to older genetic discoveries in MND – in so much that the damage is caused by lots of extra letters included in the instruction, rather than a ’spelling mistake’ in the instruction by removing, substituting or deleting individual letters. Now that genetic researchers are tuned in to looking to genetics in a new way and looking for changes in new places, it seems that there is a huge potential to make discoveries and connections that much faster. Personally I can’t wait to read the next instalment.
Read our official press release from day two of the symposium.