Our talented teams are working to advance fundamental neuroscience and harness new discoveries so that we can understand how the brain and nervous system function in health and disease.
Here, you can read about some of the research currently taking place in the institute.
- Enhancing drug discovery for MND with artificial intelligence
- Understanding childhood neurological disorders
- Investigating how the brain is affected by gluten-related disorders
Enhancing drug discovery for MND with artificial intelligence
I work on drug discovery for neurodegenerative disease using artificial intelligence (AI). The aim of my research is to use AI to identify new drugs with therapeutic potential for motor neuron disease (MND). MND is a devastating neurodegenerative disorder that affects motor neurons - the nerves that connect the brain and spinal cord to the muscles. MND is incurable and has extremely limited drug therapy options.
Astrocytes are a type of cell in the brain and spinal cord that are crucial for brain and spinal cord function. They perform many roles such as regulating blood flow and providing nutrients to nerve cells. In MND however, astrocytes go from heroes to villains: they stop supporting motor neurons and instead cause motor neuron death. This motor neuron death characterises MND, and leads to muscle weakness and paralysis.
Here in Sheffield, I use a cutting-edge cell-reprogramming technology to study MND patient astrocytes in a dish. My supervisor, Dr Laura Ferraiuolo, brought this technology to Sheffield from the US. The technology allows us to reprogram MND patient skin cells into induced Neuronal Progenitor Cells (iNPCs), which are similar to stem cells. We then convert iNPCs into brain cells such as astrocytes and neurons, allowing us to study living MND patient cells.
I use these MND patient astrocytes and grow them in a dish with motor neurons. The motor neurons glow green, and this allows us to measure their survival using a microscope. Crucially, the MND patient astrocytes are toxic to motor neurons in a dish, which captures an important aspect of the disease. I currently look for drugs that stop the motor neurons from dying and increase their survival, when grown with the MND patient astrocytes. I have also developed a ‘high throughput’ version of this experimental procedure that allows us to test hundreds of drugs a week.
I work in collaboration with Benevolent.AI - a biotechnology company who have developed state-of-the-art artificial intelligence systems. Together, we are using AI to identify new drugs that increase motor neuron survival and that could offer new treatment options for MND. We are also optimising the chemistry of these drugs so they are safe and effective. I hope that these novel drugs will go into clinical trials for MND, and my dream is to find a new drug that brings real benefit to MND patients.
I think research in brain science is so important because many diseases that affect the brain are currently incurable! I have seen Parkinson’s disease and Alzheimer’s disease affect my grandparents – and they are devastating. We have a genuine opportunity to improve the lives of patients with these types of diseases through scientific research.
Dr Matthew Stopford
Post-Doctoral Research Associate
Sheffield Institute for Translational Neuroscience (SITraN)
Understanding childhood neurological disorders
My research group focuses on early events during brain development and the consequences when these events go wrong. Half of our neurons die from programmed cell death during brain development and it is the role of the main immune cells of our brain - microglia - to clear them away. Microglia act as hoovers and their first challenge upon arrival in the brain is to clear these dead neurons. We study diseases that result in dysfunctional microglia and how they fail at clearing away dead neurons.
Humans have opaque brain tissues that develop in utero, making it very hard to study and image live. To have access to a transparent tissue available for direct observation, we use zebrafish larvae that are completely transparent.
We have shown in zebrafish that defects in the lysosomal degradation pathway, causing devastating diseases, can massively impair the ability of microglia to clear away dying neurons. This in turn creates brain inflammation and could be at the origin of brain abnormalities. We developed live zebrafish MRI to follow brain integrity in adult zebrafish. This will allow us to test therapies targeting microglia in early life and test efficacy in the adult brain.
Children affected from lysosomal storage disorders suffer from symptoms in early life and have severe disabilities associated with reduced survival. Understanding when the disease starts and what initially triggers brain abnormalities will inform on how to develop better treatments.
Dr Noémie Hamilton
ELA International Research Fellow
The Bateson Centre
Investigating how the brain is affected by gluten-related disorders
My research investigates neurological problems associated with Coeliac Disease. People living with Coeliac Disease have increased sensitivity to gluten and are advised to follow a strict gluten-free diet. As a result of repeated or uncontrolled exposure, the autoimmune response to gluten can lead to serious complications and longer term health problems for people living with Coeliac Disease.
At the University of Sheffield, we have been interested in associated neurological problems for a number of years. However, there is still a debate amongst neurologists and gastroenterologists about whether neurological damage is caused as a result of people having Coeliac Disease, with previous studies finding conflicting evidence.
Seeking to end this debate, we have now conducted a study using independent third party samples from people with no pre-existing neurological illness from the national UK Biobank. We used the samples to investigate if Biobank participants who have Coeliac Disease had any indications of brain damage compared to matched controls. This data was used to eliminate any so-called ‘ascertainment bias’ in the study.
During the study we specifically looked at cognitive test scores, answers given to questions which interrogated mental health and also conducted some brain imaging analysis. We found that the brains of people living with Coeliac Disease showed evidence of damage to brain matter and cognitive deficit in the form of slowed reaction times. Alongside this neurological damage, this group of people also had indications of worsened mental health compared to matched healthy control subjects. This is the most convincing paper to date that these problems are real.
Dr Iain Croall, PhD
Research Fellow
Department of Infection, Immunity and Cardiovascular Disease
Further information
Brain Awareness Week was founded by the Dana Alliance for Brain Initiatives (DABI) and the European Dana Alliance for the Brain (EDAB), and is coordinated by the Dana Foundation.