Principal Investigators

• Abbott
• Abrahams
• Bak
• Bastin
• Becker
• Brophy
• Chandran
• Davenport
• Gillingwater
• Gorrie
• Hahn
• Hardingham
• Jackson
• Keegan
• Kunath
• Larkman
• Lowell
• Lyons
• Miles
• Parson
• Pennetta
• Ribchester
• Skehel
• Smith
• Swingler
• Willshaw
• Wilmut
• Wishart
• Yamagishi

Cathy Abbott (Centre for Molecular Medicine)
I am a geneticist; I study a mouse strain that develops an early onset form of MND that shares many features with the adult disease. I am also very interested in what it is that makes motor neurones so vulnerable to different types of stress, when compared with other cell types in the body. If we can understand this, then maybe we can start to find ways to make motor neurones more robust.
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Sharon Abrahams (Human Cognitive Neuroscience)
Dementia occurs in up to 5% of cases of MND. This is of a fronto-temporal type and is characterised by changes in personality, behaviour and cognition. In a further 25% of cases more subtle cognitive changes can occur, predominantly involving executive dysfunction. My research has focused on investigating these more subtle cognitive impairments and on determining the brain regions which may be involved, using brain scanning techniques including positron emission tomography (PET) and structural and functional magnetic resonance imaging (MRI). In addition the research has focused on the relationship between such cognitive change and frontotemporal dementia.
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Thomas Bak (Human Cognitive Neuroscience)
My main area of interest is in cognitive and behavioural neurology. My research focuses on cognitive changes in MND, with a particular emphasis on speech and language, from the production of individual sounds and letters to the processing of complex abstract concepts. It also includes the development and optimisation of communication aids for MND patients.



Mark Bastin (Medical and Radiological Sciences / SFC Brain Imaging Research Centre)
I am a medical imaging physicist specializing in MRI methods for investigating the health of the brain's white matter. White matter plays the crucial role of linking different cortical (grey matter) regions together, and is affected in a number of diseases including MND. White matter imaging techniques that I have developed in the SFC Brain Imaging Research Centre include diffusion tensor and magnetization transfer MRI, which provide biomarkers to measure the integrity and topology of white matter tracts in vivo. Application of these imaging techniques to MND may not only provide insights into the pathophysiology of this disease, but also test the efficacy of new treatments, such as those derived from human stem cell research.
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Catherina Becker (Centre for Neuroregeneration)
Zebrafish have an amazing capacity for central nervous system regeneration. They regain function after complete lesions of the spinal cord or the optic nerve. Such lesions in mammals are not repaired and functions are permanently lost. Our research uses zebrafish to address the following questions: How can zebrafish replace lost neurones from adult stem cells? How are severed axonal connections repaired? How are these processes related to developmental neurogenesis and axonal pathfinding?
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Peter Brophy (Centre for Neuroregeneration)
I am Director of the Centre for Neuroregeneration. My research is in the field of myelination and demyelination, particularly in the role of the myelin-forming cells, the glia, in the survival of nerve fibres. This is clearly of relevance to MND because we still do not understand why nerve cells die in this disease.
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Siddharthan Chandran (Director of the Euan MacDonald Centre)
I am a clinical neurologist combining clinical activity with laboratory research. With Richard Davenport (Consultant Neurologist), I have established a multidisciplinary MND clinic in Edinburgh that will improve patient care and promote research. In the lab, my main interest is in human stem cells. Stem cells provide a terrific opportunity to study why nerves die in MND, and how we might discover and test new treatments to slow, stop or reverse this process.
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Richard Davenport (Dept of Clinical Neurosciences)
I am an NHS Consultant Neurologist, appointed in 1999. I have a variety of interests in neurology, including motor neurone diseases, and together with Professor Chandran and our MND Nurses, started up a MND clinic based in the Royal Infirmary of Edinburgh in 2009.
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Thomas Gillingwater (Centre for Integrative Physiology)
My laboratory is interested in understanding how and why motor neurones break down in motor neurone disease. Working in collaboration with a number of leading international research groups, we are examining pathological changes that occur in the nervous system during a childhood form of motor neurone disease called spinal muscular atrophy (SMA). We hope these investigations will lead to the development of novel therapeutic strategies to treat SMA and other forms of motor neurone disease.
Relevant Publication: PMID 17470424
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George Gorrie (Institute of Neurological Sciences, Glasgow; partner member of Euan MacDonald Centre)
I am a consultant clinical neurologist who has an interest in Motor Neurone Disease (MND). I help provide clinical diagnostic, therapeutic and multidisciplinary support services for patients who have this condition in the West of Scotland. As such I am driven to the development of a better understanding and treatment of this cruel disorder. I have a keen interest in the role of single gene disorders, mechanisms of aging and protein misfolding and their contribution to the pathology of MND.



Caroline Hahn (Clinical Veterinary Sciences)
My research interests are in comparative neurological and neuromuscular diseases of animals, particularly horses. Emphasis on equine neurodegenerative diseases, specifically equine motor neuron disease and equine dysautonomia.
Relevant Publication: PMID 11354647 16411586



Giles Hardingham (Centre for Integrative Physiology)
We are interested in signals and genes that influence the survival of neurons. In particular we investigate how synaptic activity can regulate the expression of these genes and influence neuronal viability. Oxidative damage is associated with the pathophysiology of a number of neurodegenerative diseases, including those affecting motor neurones. Much of our work focusses on the control of neuronal antioxidant defences by synaptic activity and other signal pathways.
Relevant Publication: PMID 16641230
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Mandy Jackson (Centre for Integrative Physiology)
My lab focuses on identifying the cellular mechanisms that underlie the death of nerve cells involved in movement coordination. We are using an animal model of disease to understand what biological pathways are impaired and in doing so identify therapeutic strategies that could prevent or slow down disease progression.
Relevant Publication: PMID 16274998
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Liam Keegan (MRC Human Genetics Unit, Edinburgh)
We are investigating the role of RNA editing and glutamate excitoxicity in ALS and other neurodegenerative diseases. RNA editing of transcripts encoding ionotropic glutamate receptor subunits controls many aspects of AMPA and kainate receptor function. Reduced RNA editing of the Q/R editing site in the GluR-B transcript leads to increased calcium permeability of AMPA receptors and has been reported in motor neurones in Japanese sporadic ALS patients.
Relevant Publication: PMID 14757529
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Tilo Kunath (MRC Centre for Regenerative Medicine and Institute for Stem Cell Research)
Our group is interested in understanding the molecular mechanisms important for the induction of primitive neural tissue from naïve ectoderm. We are currently investigating the roles of fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signaling on neural induction of embryonic stem (ES) cells. This will give us an understanding of how to differentiate mouse and human ES cells into neural tissue that may used to study and treat diseases of the nervous system, such as motor neuron disease.
Relevant Publication: PMID 17660198
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Phil Larkman (Biomedical Sciences BMTO)
I am interested in the mechanisms by which motoneurones integrate synaptic information form the basis of my research interests. I am interested in how voltage-gated ion channels, including several classes of potassium (K ) channel and the hyperpolarisation-activated current, Ih, influence synaptic integration in the dendrites of motoneurones and, in particular, the functional importance of the modulation of these channels by aminergic (5-HT, noradrenaline) neurotransmitters.
Relevant Publication: PMID 15733086



Sally Lowell (MRC Centre for Regenerative Medicine and Institute for Stem Cell Research)
We work with embryonic stem cells, devising ways to convert them into neurons. We aim to understand the molecular mechanisms that drive this process, and to use this information to develop strategies for improving neural repair or for testing candidate neuroprotective drugs.
Relevant Publication: PMID 16594731
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David Lyons (Centre for Neuroregeneration)
I am a neurobiologist with a background in developmental biology and the genetics of nervous system formation and function. My group uses zebrafish as a laboratory model organism. Zebrafish are a useful system because the early development of their nervous system is strikingly similar to that of higher vertebrates. They also provide the capability to observe cell behaviour at high resolution and understand gene function in the intact living animal, which is very difficult in other laboratory systems. As part of our work, we are particularly interested in the mechanisms that regulate the transport of factors along nerve cell processes, which is crucial for normal nervous system function, and is disrupted in numerous neurodegenerative diseases, including motor neurone disease.
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Gareth Miles (Lecturer, University of St. Andrews; Partner member of Euan MacDonald Centre)
My laboratory studies how the spinal cord controls movement by analysing the electrical activity of individual neurons and the connections they form with each other. My laboratory also examines changes in the properties of neurons and their connections that occur due to diseases such as MND. Through our research, we hope to explain why motor neurones selectively die in MND, and to reveal targets for new treatments of MND.
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Simon Parson (Centre for Integrative Physiology)
I am a basic scientist and my laboratory works on the connections between the brain and muscle (neuromuscular junctions). These important connections are amongst the first to be damaged in a variety of motor neurone diseases. We aim to understand the factors that determine why these connections are vulnerable, how we might intervene to strengthen them and thereby prolong the active life of sufferers.
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Giuseppa Pennetta (Centre for Integrative Physiology)
I am a molecular geneticist. The major focus of my research is the study of the molecular mechanisms underlying the pathogenesis of MND, using the fruit-fly Drosophila melanogaster as a model organism. The high degree of similarity in genetic function and molecular pathways between Drosophila and humans has made this organism an extremely versatile model for the study of human biology and neurodegeneration in particular. We generated a fly model for motor neurone disease and we are currently using it to elucidate the mechanisms of this devastating disease. We are confident that this approach will lead to the identification of potential new targets for effective therapeutic interventions.
Relevant Publication: PMID 11832215 12160747



Richard Ribchester (Centre for Neuroregeneration and Centre for Integrative Physiology)
I am Professor of Cellular Neuroscience and my main research interest is in the connections between motor neurones and muscle. Synapses at these neuromuscular junctions are the first to degenerate in many forms of Motor Neurone Disease, including common forms of MND. We combine electrophysiological techniques and imaging to find out how this synaptic degeneration is triggered and to explore ways that it could be slowed down or completely prevented using gene-based therapies, drugs or exercise. We are also working on ways to apply new imaging technologies to observe living neuromuscular junctions and to diagnose, monitor and treat the progression of MND.
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Paul Skehel (Centre for Integrative Physiology)
What actually causes cells to die in most neurodegenerative diseases is not understood. Some cases of disease are caused by a mistake, or mutation, in a specific gene. I study how such mutated genes affect nerves and other cells in the body, hoping to identify biological processes that may be manipulated to slow down or arrest degeneration.
Relevant Publication: PMID 15372378
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Colin Smith (Centre for Clinical Brain Sciences)
I am a clinical neuropathologist and much of my research is centred around brain banking and improving the quality of tissues in human brain banks. Developing a national brain bank facility for MND is a key goal of this activity as translational studies linking experimental data, human tissues and clinical experience are core to the development of new therapies in MND.
Relevant Publication: PMID 16484645



Robert Swingler (Consultant Neurologist, Ninewells Hospital, Dundee; Partner member of Euan MacDonald Centre)
I am a clinical neurologist based in Dundee. I set up the Scottish MND register in 1989. Because this was the first national register of the condition it was the first study to provide a clear idea of the number of people being newly diagnosed every year. It was also the first study to provide information about quality of care nationally. The register was later used to identify people who wished to participate in trials.



David Willshaw (School of Informatics)
I am interested in the application of the methods of computational neurobiology -- mathematical analysis and computer simulation - to an understanding of the development and functioning of the nervous system. One of my specific areas of interest is the mechanisms of elimination of polyinnervation in developing muscle and its possible relationship to synaptic degeneration in motor neurone disease.
Relevant Publication: PMID 10966757
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Ian Wilmut (MRC Centre for Regenerative Medicine)
My objective is to understand key regulatory mechanisms during early embryo development and to use that knowledge to establish new approaches to the study of inherited human diseases. The nuclear transfer techniques in animals established that complete reprogramming of an adult somatic cell nucleus is possible, but a rare event. Furthermore these methods have not been extended to humans. By understanding the molecular events that are involved it may be possible either to increase the efficiency significantly or to establish methods for reprogramming cells from adults without making an embryo. Either of these methods for producing embryo stem cells from patients would provide important new opportunities to study inherited diseases such as ALS with the longer term aim of developing new treatments.
Relevant Publication: PMID 16352868
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Tom Wishart (Division of Neurobiology; The Roslin Institute)
My laboratory is interested in understanding what makes specific neuronal populations vulnerable to various neurodegenerative stimuli. We combine anatomical knowledge, high-resolution imaging and biochemical/molecular biological techniques to elucidate the mechanisms underpinning altered neuronal vulnerability. We anticipate that these approaches will ultimately lead to the identification of novel therapeutic targets that may prove effective modulators of disease progression across multiple neurodegenerative conditions.
Relevant Publication: PMID 20705736 19640925 17470424
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Junichi Yamagishi (Centre for Speech Technology Research)
I am a speech scientist who mainly works on speech synthesis technology, which is the conversion of written text into speech output. I developed a 'voice cloning' system that can create new synthetic voices from just a few minutes of recorded speech. The technology can be successfully applied to clinical voice banking and voice reconstruction for patients who have lost or are losing their voices due to conditions such as MND or Parkinson's disease.
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