Martha McLaughlin, UCL Institute of Neurology

Understanding the mechanisms of motor neurone disease (PhD studentship)

Martha McLaughlin was awarded a place on the prestigious four-year Clinical Neurosciences PhD programme at UCL Institute of Neurology in 2016, funded by Brain Research UK.

The first year of the Clinical Neurosciences PhD is a training year, in which students attend some specialised courses and do three short research projects in different labs. This helps them to gain experience and build expertise across different areas of neuroscience. They then choose a supervisor and develop a full research project for the subsequent three years.

Having completed her training year, Martha opted to pursue research into amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease. She is working under the supervision of Professor Linda Greensmith and Dr Pietro Fratta to understand more about the role of a protein called TDP-43 in ALS.

About ALS

Like other forms of motor neurone disease (MND), ALS is a fatal, rapidly progressing disease that attacks the nerves that control movement (motor neurones). This affects muscle function, initially causing weakness and wasting before progressing to severe paralysis and breathing difficulties.

There is no cure for ALS or other forms of MND. A third of patients die within a year of diagnosis and more than half within two years.

Read more: Motor neurone disease                                   

The role of TDP-43 in ALS

The causes of ALS are not fully understood, but there is evidence suggesting that a protein called TDP-43 is involved in the disease mechanism. TDP-43 is normally found inside the nucleus of healthy cells but abnormally accumulates outside the nucleus of nerve cells in most patients with ALS.

Additionally, it has been found that a mutation in the TDP-43 gene, responsible for production of TDP-43 protein, is the cause of a small proportion of all ALS cases.

TDP-43 is an important protein that plays a role in the processes through which the instructions contained within our genes are translated. Genetic code is translated into proteins via messenger molecules known as RNA.

In healthy cells, TDP-43 protein binds to RNA and is involved in RNA processing and maturation. Disruption to TDP-43 can have a profound effect on the cell, as it disrupts the function of RNA, which in turn affects the production of proteins.

Martha and colleagues are investigating how the metabolism of RNA is altered in cells with different mutations in the TDP-43 gene. These mutations may cause the resulting TDP-43 protein either to be less functional or to develop new functions that the normal TDP-43 protein does not have.

Impact

This work will give a greater insight into the role played by TDP-43 dysfunction in the causation of ALS.

Better understanding of the mechanisms underlying the development of the disease is essential if we are to find ways to not only treat the symptoms of ALS but potentially to develop a cure for ALS.