Our Fellows

TDP-43 is a protein important for the specific transport of RNA to different locations in the axons and in the response of cells to stress and damage. This project will combine novel mouse models and patient cell lines to investigate how TDP-43 impacts the response of motor neurons to damage in the axons, and the relevance of this response pathway in ALS. It will help to understand how changes in TDP-43 impact motor neuron survival. This information will be essential to develop effective therapeutics. 

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October 2019 - September 2024                                                                                             

The project aims to study people carrying genetic alterations that predispose to MND in the years before symptoms begin. By measuring the levels of thousands of proteins in cerebrospinal fluid – the fluid closest to the cells affected by MND – Dr Thompson aims to detect MND-related changes occurring in the nervous system long before the start of MND symptoms. This will hopefully shed light on the mechanisms that lead to the development of MND, paving the way for new therapies, and develop ways of predicting when MND will begin in order to allow earlier treatment of MND – even before symptoms develop.                        

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April 2020 - April 2025

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MND is a highly complex disease and can affect each individual differently. This variability may be the reason for the failure of many clinical trials in the past. In a couple of previous clinical trials, further analysis of these “failed” trials showed that the treatment may be beneficial for smaller subgroups of people with MND rather than the whole cohort. This project will study proteins in people with MND to try to understand what is happening within the nervous system that would account for the differences in the way MND affects people. Using computer models the project aims to identify patterns which could potentially create subgroups of MND.  This project aims to categorise people with MND into disease subgroups, which could potentially improve the chances of finding effective therapies by helping to select ‘the right patient for the right trial.’ 

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August 2023 - September 2025         

MND is an ‘energy hungry’ disease meaning that people with MND burn more energy due to an increased metabolic rate. The brain and central nervous system (CNS), which includes motor neurones and the spinal cord, need a lot of energy they are constantly communicating with each other and the rest of the body. In MND, it has been suggested these cells may not be getting the amount of energy they need to function properly and this could lead to cell damage. This project will be looking into this idea and assessing what happens to the cells in the brain and CNS when they are starved of energy. The study also aims to investigate the relationship between cells in the spinal cord to understand more about the biological pathways that might be impacting the production of energy in the body, and how these pathways are different in MND.

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September 2023 - August 2028 

• Prof Martin Turner (University of Oxford) | August 2008 - July 2013 and August 2013 - August 2018
• Dr Robin Highley (University of Sheffield) | February 2009 - January 2012
• Dr Ceryl Harwood (University of Sheffield) | April 2009 - March 2012
• Dr Pietro Fratta (University College London) | Sep 2010 - August 2013 and April 2015 - March 2019
• Dr Johnathan Cooper-Knock (University of Sheffield) | September 2012 - September 2015
• Dr Jemeen Sreedharan (University of Massachusetts Medical School and the Babraham Institute) | June 2013 - February 2018
• Dr Jakub Scaber (University of Oxford) | August 2013 - August 2016
• Dr James Bashford (King's College London) | October 2016 - September 2019
• Dr Emily Feneberg (University of Oxford) | October 2017 - August 2019
• Dr Arpan Mehta (University of Edinburgh) | August 2017 - January 2021
• Dr Rickie Patani (University College London and The Francis Crick Institute)  | March 2019 - February 2024

An additional Clinical Fellowship was co-funded with MND Scotland and the Scottish Government Chief Scientist’s Office:

• Dr Danielle Leighton (University of Edinburgh) | August 2015 - August 2018

Glial cells, a type of cell found in the brain and spinal cord, help to ensure that neurons are functioning correctly and maintain connections between neurons and muscles. In some neurological diseases, glial cells become toxic and consume synapses (connections which enable messages to be sent from one neuron to another to be passed to the muscles) causing these connections to be lost. This project aims to investigate the link between toxic glial cells and synapse loss in MND using cell models and brain tissue to observe the action of the toxic glial cells on synapses. It will provide new insights into the role of glial cells in MND and may potentially highlight ways to delay or prevent synapse loss which could help to slow the progression of the disease.

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February 2022 - July 2024

While research into MND has improved our understanding of what is changing within the motor neurons in the disease, current knowledge of why these changes occur is limited. One of these changes is the incorrect processing and placement of a molecule called RNA, which is a photocopy of DNA that is used to make proteins in cells. The main aim of this project is to investigate whether a class of small RNA molecules, known as miRNA, are affected in MND and, if they are, whether they are a cause or consequence of the disease. Identifying the miRNA molecules affected in MND and how they change could help to reveal a potential treatment strategy.

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August 2022 - August 2024

Currently, we do not know the best way to subgroup and classify neurodegenerative diseases since overlapping disease mechanisms are often not taken into account. This project involves reclassifying these diseases based on a combination of biological measures. This will include genetic profile, epigenetics (a system controlling whether genes are switched on or off) and the level of a nerve protein found in the blood called neurofilament. The variations of these three areas will be analysed for both MND and Frontotemporal dementia (FTD) and machine learning will then be used to find patterns that correspond to different subgroups. If this allows for the formation of new subgroups, these can be used group people with MND together for clinical trials and to understand the underlying biology of the conditions.

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January 2022 - September 2024

MND affects people in different ways, with symptoms emerging and progressing at highly variable, unpredictable rates. Therefore, some treatments may work in some people with MND but not in others. It is now established that those with the disease often experience cognitive and behavioural problems. The aim of this project is to develop ways to measure brain function changes that can predict patient symptoms and improve understanding of the biology of why MND has different effects on different people. This is expected to facilitate earlier, more informative diagnoses and improve detection of effective therapies in clinical trials.

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April 2021 - September 2024

FUS is a protein that regulates the production of other proteins and is known to be dysfunctional in MND. This project aims to understand how the disruptions to protein production caused by FUS alter the function of nerve cells and their connection to muscles. Once it is understood how nerve cells are damaged, the project will move on to investigating if it is possible to correct this damage. Understanding the changes to nerve cells in MND is crucial to designing new and effective treatments.

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September 2022 - August 2025

Some cases of MND are caused by a build-up of a protein called TDP-43, which clumps together to form toxic “aggregates”, leading to motor neuron damage and death. The differences in symptoms and severity between people with MND may be partly due to differences in aggregates of TDP-43. A custom-designed technology has been developed that allows the features of aggregates to be seen in high levels of detail so they can be characterised by similar features.  Dr Saleeb’s project will use this state-of-the-art technology to characterise the differences between different TDP-43 aggregates in post-mortem tissue. This information will be used alongside knowledge of how the disease developed to identify different aggregate types and investigate their use as early markers of disease prognosis.

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April 2023- March 2026

Some people with MND experience cognitive or behavioural symptom and also have frontotemporal dementia (FTD). Previous research has suggested that these symptoms may have a genetic cause. However, currently little research has been done to identify which genes and pathways might be involved. Dr Byrne’s fellowship project will analyse data from the largest studies of genetic factors contributing to MND and cognitive symptoms to identify shared genetic factors (which contribute to both cognitive decline and MND) and distinct genetic factors (which contribute purely to motor symptoms in MND). It is hoped that this could help with grouping people with MND for clinical trials, and in understanding the causes of cognitive symptoms in MND.

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September 2023- August 2026

Tiny structures on the surface of brain, called membrane lipid rafts, play an important role in this communication. Previous research has shown that these structures do not work properly in models of a specific genetic type of MND, called SOD1 MND, and that the function of the  rafts could be boosted using a protein (caveolin-1) which protects nerve cells. Dr Moll's research aims to investigate if membrane lipid rafts are also faulty in other genetic types of MND and test whether increasing the production of caveolin-1 could reduce damage to nerve cells.

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April 2024 - March 2027

Some proteins can become ‘lost’ in MND and move from the nucleus of the cell, where they should exist, to another part called the cytoplasm. This movement of proteins mean that they are no longer able to function as they should and this can have many effects including the corruption of RNA messages created from DNA. Dr Wang's fellowship project will use cell models of MND to understand more about the biological mechanisms that underlie the misplacement of proteins within neurons. It will also look at how these mechanisms might contribute to the development and progression of MND.

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May 2024 - April 2027

In the most common form of genetic MND, C9orf72, the gene changes lead to the production of toxic proteins called dipeptide repeat proteins (DPRs). These toxic proteins disrupt the movement of other proteins between different parts of a motor neuron. TDP-43 is one of the proteins which is impacted by dipeptide repeat proteins and is thought to play a key role in motor neuron death. TDP-43 gets stuck in the wrong area of the motor neuron and becomes faulty. Dr Solomon's fellowship project aims to understand why dipeptide repeat proteins disrupt the movement of proteins like TDP-43 and if there is a way of correcting their movement in MND. 

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July 2024 - June 2027

• Dr Scott Allen (University of Sheffield) | January 2016 - March 2019
• Dr Martina Hallegger (University College London) |  January 2016 - December 2019
• Dr Ashley Jones (King's College London) | March 2016 - August 2019
• Dr Russel McLaughlin (Trinity College Dublin) | January 2016 - September 2019
• Dr Matt Gabel (Previously University of Sussex, now at the University of Oxford) | July 2017 - June 2019
• Dr Patricia Gomez-Suaga (King's College London) | May 2018 – July 2021
• Dr Barney Bryson (University College London) | August 2017 - September 2022
• Dr Andrew Tosolini (University College London) | November 2021 - April 2023
• Dr Daniel Scott (University of Nottingham) | August 2019 - January 2024
• Dr Gareth Wright (Previously at University of Liverpool, now at University of Essex) | April 2019 - March 2024
• Dr Tatyana Shelkovnikova (Previously at Cardiff University, now at University of Sheffield) | September 2018 - June 2024