Web logs and lab work
An illustration of Alzheimer’s disease by artist Stephen Magrath
The Wellcome Trust/ MRC-funded Neurodegenerative Diseases Initiative, conducts collaborative research into Parkinson’s, Alzheimer’s and Motor Neuron Diseases. Emma Daniel, a Postdoctoral Fellow in the Department of Clinical Neuroscience at King’s College London, tells us more about the Initiative and introduces their latest project: new blog Degenerating Neurons.
Alzheimer’s, Parkinson’s, dementia. Perhaps your elderly neighbour is affected, maybe your Nan. As more of us than ever before live to ripe old ages, degenerative brain disease, or neurodegeneration, is affecting more and more people. The MRC/ Wellcome Trust “Neurodegenerative Diseases Initiative”, launched in 2009, funds three distinct brain disease research teams, and promotes collaboration between them to achieve a greater understanding of the biology underpinning all neurodegeneration.
There is an increasing recognition that many neurodegenerative diseases share common features. Research findings from the Parkinson’s disease field mirror those found independently in the Alzheimer’s disease field – proteins “mis-fold” or form toxic structures and clumps in both diseases. And research shows that some of the same proteins are involved in a number of different diseases. TDP-43, for instance, is a protein whose clumping in the brain can be seen in frontotemporal dementia, motor neuron, Parkinson’s and Alzheimer’s diseases and others.
My work investigates TDP-43. TDP-43 normally lives in the nucleus of all our cells, where our DNA is coiled up into chromosomes. Its function is to transport and edit messenger RNA, which is a “photocopy” of our DNA, used as a blueprint for making proteins. In 2006 it was found that TDP-43 formed large clumps in the brain cells of people with frontotemporal dementia and in the spinal cells of people with motor neuron disease. For the first time it was clear that these two very different diseases, a dementia and a movement disorder, were linked mechanistically.
My research is helping to determine why TDP-43 builds up and forms clumps, and whether this process might be reversed. The clumps themselves may not cause the death of brain and spinal cells, but by drawing in the TDP-43, they may prevent it from fulfilling its vital role in transporting RNA. I use cells grown in a dish to investigate how TDP-43 levels are regulated- particularly how the cell’s garbage disposal system makes sure TDP-43 supply and demand are matched, recycling excess TDP-43 so that it doesn’t build up.
I became interested in the processes of protein “turnover” during my PhD studies at the University of Auckland in New Zealand, under Associate Prof. Michelle Glass, Prof. Mike Dragunow and Prof. Richard Faull. My work there used cells in a dish to model Huntington’s Disease, another degenerative disease characterised by the build up and clumping of protein in brain cells. The protein was different, the specific areas of the brain affected were different, and the clinical outcome for patients was very different, yet the similarities at the molecular level between Huntington’s and motor neuron disease led me to seek my current position under Prof. Christopher Shaw at KCL.
Prof. Shaw’s group is part of a consortium of labs across the UK and internationally which study the role of RNA processing proteins in degenerative brain diseases, particularly motor neuron disease and frontotemporal dementia. Together with another consortium investigating the mechanisms by which amyloid proteins are toxic in Alzheimer’s, and a consortium which studies Parkinson’s Disease, we form the Neurodegenerative Diseases Initiative. By bringing together researchers working on different neurodegenerative diseases, this MRC- and Wellcome Trust-funded initiative will ensure a greater understanding of the commonalities between these diseases, and accelerate research towards their treatment.
The initiative is UK-driven but encompasses labs across the globe, with groups from the University of Cambridge, King’s College London, University College London, University of California, University of Dundee, University of Manchester, University of Sheffield, University of Bristol, University of Toronto and the Max Planck Institute (Bonn). Being part of this consortium has exposed me, as a relatively junior postdoctoral researcher, to innovative new methodology from other fields, given me the inside scoop on where these fields are moving, and challenged me to put my research into the perspective of neurodegeneration as a whole.
We work closely with colleagues across the consortium on specific research projects, but our new blog has allowed us to collaborate on a more personal level. The Degenerating Neurons blog explores exciting recent developments in neuroscience research, both from within the initiative and elsewhere. We cover all sorts of different subjects – from the creation of brain cells from patient skin cells, to tracking down a gene which triples the risk of Alzheimer’s Disease. Beautiful brain imagery abounds, and scientific discoveries come to life, as our clinicians, researchers and postgrad students all turn their hand at blogging for the non-scientist reader.
As well as sharing research findings with the public, our blog also details the production, currently underway, of a short film about our brain disease research. The film is due to be launched at a public symposium on March 13th 2013, during Brain Awareness Week, details of which can be found on the blog.
The Neurodegenerative Diseases Initiative has gone a long way to bridging the gap between different fields of brain disease research in the UK. Now we look forward to sharing our work with the public who fund it, and who we hope will benefit from it.
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