Driving MND Research through our Senior Non-Clinical Fellowships

Driving MND Research through our Senior Non-Clinical Fellowships

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Each year, MND Associations across the globe mark 21 June as a special day of recognition, acknowledging the impact that MND has on people around the world. MND is a global problem. It does not discriminate, and for every person diagnosed the effects of the disease will be forever felt by their families and friends.

In this week-long series of blogs, in acknowledgement of the work carried out by researchers and the support given by the wider MND community, and to mark Global MND Awareness Day, we will be taking a closer look at the research funded by the MND Association and how this is #DrivingMNDResearch.

As of 31 May 2021, the Association is funding, with support from the Wolfson Foundation and other donors, eight Non-Clinical Fellowships with a value of £1.9 million. The Lady Edith Wolfson Fellowship Programme attracts and develops the careers of outstanding young Clinical and Non-Clinical researchers in order to create the future scientific leaders in the field of MND Research. In this blog, we will be taking a closer look at the work being carried out by four of our Senior Non-Clinical Fellows, as well as hearing from a previous Senior Non-Clinical Fellow, and finding out what the Fellowship programme means to them.

Meet our Senior Non-Clinical Fellows

Dr Tatyana Shelkovnikova is aiming to understand the connection between RNA-protein droplets, called paraspeckles, and motor neuron malfunction. An RNA molecule called NEAT1 forms the scaffolding of small compartments in a cell’s nucleus (called paraspeckles). It has been suggested the way NEAT1 is created may be altered and that these changes might be common to both sporadic and familial MND and differentiate them from frontotemporal dementia (FTD). This project will model NEAT1 in human motor neurons and fruit flies and observe how it responds to stress and toxicity within neurons. Understanding the adverse processes regulated by NEAT1 might provide a potential target for therapy.

When asked how the Fellowship programme has helped her, Tatyana said:

Dr Gareth Wright is from the University of Liverpool. His project will help us to understand what causes SOD1 misfolding in MND and find therapeutic applications.

SOD1 is a protein found in all human cells but sometimes it misfolds into abnormal shapes that are toxic to motor neurons. The team will search for drug molecules that help the SOD1 protein fold properly and create synthetic proteins that will remove it using the cellular recycling system.

We asked Gareth what the Senior Non-Clinical Fellowship meant to him and he said:

The MNDA’s Senior Non-Clinical Fellowship has given me the time and resources to direct my own research and become established as an independent scientist. 

Dr Scott Allen, from the University of Sheffield, was one of our first researchers to be awarded a Senior Non-Clinical Fellowship. His work is focusing on metabolic dysfunction – when there is a problem with the way that energy is produced and used within motor neurons – and how it might influence disease progression. The part of the motor neuron that is responsible for energy supply and use is called the mitochondria. His project aims to use stem cells from people with MND and turn them into motor neurons and astrocytes, which help provide energy to motor neurons. These cells will be used to observe abnormalities in the mitochondria and further our understanding of what is going wrong with energy processes in motor neurons. The project will also use a fruit fly model of MND to assess these mitochondrial alterations. This will allow any possible therapeutic targets to be identified which may help to combat the metabolic dysfunction seen in MND.

Explaining how the support from the Fellowship helped him, Scott said:

He went on to say:

“The scheme was absolutely fundamental in my transition from an aspiring post-doctoral researcher to a young academic and PI. It was a great honour to be part of the first cohort of Non-Clinical Fellow’s and I will be eternally grateful for all the support the MND Association has given me over the years.”

The work being carried out by Dr Barney Bryson, from University College London, is contributing to the development of a potential new therapy by replacing damaged motor neurons and restoring lost muscle function. This project uses stem cells from mice transformed into motor neurons which will be used to create new muscle neuron connections.

These cells will be implanted back into the mice and observed to see how well the neurons connect with muscles. The researchers will then identify the chemicals that promote successful innervation.This study has the potential to contribute to the development of a new therapy by replacing damaged motor neurons and restoring lost muscle function.

When asked about how the Fellowship is helping to drive MND research, Barney told us:

“The senior non-clinical fellowship has been a tremendous springboard to not only drive my research project forward but, importantly, it has also set me on the path towards a fully independent research career. I have received incredible support from the Association throughout the duration of my Fellowship and, in particular, during the difficulties that all researchers have faced over the past year, which I am extremely grateful for. Most importantly of all, the generous support from the MND Association has enabled me to make great strides in advancing an extremely exciting and novel therapy aimed at overcoming lost muscle function for MND patients.” 

One of our past Senior Non-Clinical Fellows, Dr Martina Hallegger from University College London, told us about her work and how the Fellowship programme has helped her take her research to the next stage.

“I would like to thank the MND Association for so generously supporting my work. I was awarded the Lady Edith Wolfson Senior Non-Clinical Fellowship in 2016, which has allowed me to develop my research in the exceptional environment of the Department of Neuromuscular Diseases at the Institute of Neurology, UCL. I’m part of an amazing team of fundamental and clinical researchers like Prof Ule, Prof Patani* and Prof Fratta*, with whom I closely collaborate and who are a daily inspiration. Coming from a background in fundamental research in RNA biochemistry and transcriptomics, I was thrilled to apply this skill set to some foundational questions in the field of motor neurone research. For example, I explore how mutations in TDP-43, the protein central to the pathology, change the way that TDP-43 interacts with its RNA targets. It has been known for a while that TDP-43 regulates the fate of many genes, but we didn’t know what features would make these genes vulnerable once the disease begins. We have just submitted a major manuscript where we have dissected how TDP-43 can form droplets on some RNA regions, including its own message, and how these droplets become unstable when TDP-43 is mutated.  This reflects a change in the ability of TDP-43 to bind to itself to form larger complexes. The astonishing thing is that TDP-43 does not interact with all RNAs like this. This is why only my global transcriptomics approaches allowed me to decipher the underlying RNA code, which consists of very long stretches of RNA that have many similar binding sites crowded together.  Together with the computational team we have developed computational analysis pipelines to analyse this kind of data even better, which will benefit the wider scientific community.”

*Profs Patani and Fratta are two of our current Lady Edith Wolfson Clinical Fellows.
“This fellowship has empowered me to pursue this exciting project.  Not only have I been supported very generously by the MND Association, but the charity has always kept in touch, and come for regular visits to the Francis Crick Institute where the lab is currently located.  Their International Symposium is a crucial annual event highlighting the major advances in the field and providing great networking opportunities.  
I’m now taking this project to the next stage to ask specifically what happens transcriptome-wide in motor neurons when TDP-43 is mutated, and how can we harness the RNA fragments that have these special features, for therapeutic means?  There are very exciting times ahead!”

Five decades of research

The Association’s commitment to understanding MND and the relentless search for treatments is now in its fifth decade. We will not stop until we have reached our vision – a world free from MND.

How can you get involved?

You can help us increase awareness of MND research by sharing any of the Association messages which will be posted across Twitter, Facebook, and Instagram using the hashtag #DrivingMNDResearch. Please share your involvement with the MND Association and the invaluable part you play in #DrivingMNDResearch.

You can also:

For more information and to download our #GlobalMNDAwarenessDay graphic to use, head to our website.

The MND Community is a passionate, dedicated and focused team of people contributing expertise, time and money to the collaborative effort to find treatments and ultimately a cure for this brutal disease.

We are proud to work with every one of you and thank you for your continued support.

Read more about the research we fund on our website

Read more about our Fellowship programme and our Fellows

The MND Association’s vision is a world free from MND. Realising this vision means investing more in research, further developing partnerships with the research community, funding bodies and industry, while ensuring that advances in understanding and treating MND are communicated as quickly and effectively as possible. Our Research Development team, composed of 11 members, work hard to achieve this. Principally, the Research Information team within this are involved in communication activities including this MND Research blog.