This initiative is providing researchers with the opportunity to establish cross-discipline collaborations and to develop synergistic programmes of research. Six projects of approximately 12 months’ duration will build study cohorts, engage with researchers from disciplines not represented within the BRC and identify opportunities for the BRC to work with internal and external partners.
PI: Dr Joseph Inns
Researchers are now using advanced research techniques to identify and study single cells using healthy human tissues, as well as from diseased tissue from patients with health conditions. This can give new understanding as to why these diseases happen, and lead to advances in patient care.
This project plans to develop a method that takes advantage of these technological advances in order to allow the detailed study of a rare genetic skin tumour condition, called CYLD cutaneous syndrome (CCS).
It will pilot the interdisciplinary interaction between dermatology and proteomics labs and across the BRC Neuromuscular Disease, Rare Diseases and Mitochondrial Dysfunction, and the Skin Disease, Oral Disease and Immunogenomics themes.
In the course of this work, the team aims to develop a novel methodology for single cell proteomics and also identify specific cell populations that are responsible for causing or sustaining these skin tumours. This will have the dual advantage of the developing both novel insights into this disease and a methodology that will advance the study of other rare and common human diseases. Once established in skin, the team plan to test their approach in samples taken from patients with muscle disease. The methods will be shared as a publicly available resource for the benefit of other researchers, brining wider benefits.
PI: Dr Joanna Elson
Creating predictive tools from patient data can provide valuable insights into future health outcomes for the benefit of both individuals, families and healthcare providers. Evidence suggests that looking at the genetic instructions found within the cells of our body can help make predictions about how a condition may change over time and help identify suitable medicines or treatments. This is done by studying many different genes within an individual at the same time, which allows a number called a ‘polygenic risk score’ (PRS) to be determined based on the variations seen within the genes. For organisations like the NHS, having access to this score has potential to help move away from a more conventional ‘one size fits all’ approaches to treatment and support the delivery of precision medicine that takes into account individual genetic variation to improve patient care and treatment options.
Mitochondria are energy-generating structures found within the cells of the body that contain their own genetic instructions called mitochondrial DNA (mtDNA). a score for some of the mtDNA genes present within the mitochondria, which has reported a difference between patient and control groups for several conditions, including Chronic Fatigue Syndrome. The aim of this BRC funded project is to further improve this score by looking at all of the mtDNA genes to better predict fatigue levels in a variety of long-term conditions where low energy is an important feature, including mitochondrial disease, Sjögren’s syndrome and rheumatoid arthritis. During the lifetime of the project, the team will explore if the enhanced mtDNA PRS can be used to predict both the course and severity of these conditions. The hope is that this will support health care decisions for patients living with these devastating and highly debilitating conditions both in Newcastle, across the UK and beyond.
This interdisciplinary bid will bring together the depth and breadth of world class fatigue and associated phenomena, and PRS research from the Musculoskeletal Diseases and Inflammation Medicine Theme, the Neuromuscular Disease, Rare Diseases and Mitochondrial Dysfunction Theme and the Digital Health, Ageing Innovation, and Inclusion Theme.
PI: Prof Edward Meinert
This project is bringing together expertise from the Digital Health, Ageing Innovation and Inclusion Theme, the Dementia, Mental Health and Neurodegeneration Theme, and the Informatics and Precision Care for an Ageing Population Theme to combine clinical mental health research with software engineering to develop a digital health solution.
There is an increasing burden of mental health issues on the healthcare system, which is straining the capacity of mental health services and professionals, especially in the wake of the COVID-19 pandemic. Early onset disorders, like bipolar disorder, can have a significant and increasing impact on patients’ overall health and well-being as they age (for example, by increasing risk of dementia and other conditions). By helping patients learn to manage their condition from a young age, early interventions have the potential to reduce the impact of mood episodes over their lifetime. Digital tools, such as mobile apps, can be easily and privately accessed by people who may otherwise be unable or unwilling to seek mental health support services.
The project team previously conducted research on how to use mobile health apps to help young people monitor and manage symptoms of bipolar and other mood disorders. This project will build off that work to design a prototype for a digital health intervention. Since the initial work in 2016-2017, the capabilities of digital interventions have significantly advanced. The project team will improve this intervention by conducting a series of workshops with young people, their family and carers, and healthcare professionals. These will aim to identify their needs – and how these might have changed since the previous study – and to co-produce improvements to the app to incorporate technological advancements and new suggestions. They will evaluate how the patient’s carers (a diverse population including older adults) interact with this technological approach to mental health monitoring and explore the implications for re-using this app for similar interventions in different populations (e.g., monitoring the mental health of older adults). The refined app, that will be designed by the end of this project, can then be developed and evaluated for acceptability, usability, and real-world impact in future evaluations.
PI: Dr Claire McDonald
This study will bring together the interdisciplinary expertise of four NIHR Newcastle BRC Themes. It will build on the Ageing, Sarcopenia and Multimorbidity Theme, the Digital Health, Ageing Innovation and Inclusion Theme, the Dementia, Mental Health and Neurodegeneration Theme and the Musculoskeletal Disease and Inflammation Medicine.
The project is an exemplar of how combining expertise across Themes will deliver insights in a complex area describing the interplay between muscle weakness, depressive symptoms and fatigue and the resultant effect on physical activity.
Getting older is associated with the development of multiple long-term health conditions (MLTC). Low mood, tiredness (fatigue), and muscle weakness are commonly reported by people living with MLTC. People living with MLTC are also less active than those without MLTC and find day-to-day activities difficult.
Previous research has tended to examine these issues in isolation or focus on how social factors may explain these conditions. However, it is likely that all of these issues are linked and have shared underlying biological causes. Long-term conditions are more common as we age, so it is likely that the causes of long-term conditions are related to ageing. It is suspected that these causes of ageing also partly cause low mood, fatigue and muscle weakness. Understanding how the causes of ageing also cause these conditions is the purpose of this study.
The team will recruit 60 people from the MULTIPLE Registry – a database of people living with MLTC who have expressed interest in taking part in research. They will ask participants to complete questionnaires about their health, social circumstances, mood and fatigue. Participants will complete tests of muscle strength, endurance, and muscle size. The team will then measure daily activity over a week by using a small sensor attached to the lower back. Finally, they will collect blood samples to measure a series of blood tests that are markers of different causes of ageing.
If successful, this initial study will pave the way for larger studies to look at the relationship between MLTC and ageing in more detail. Studies like this could identify new targets for treatments to improve muscle strength, fatigue and mood all with a single treatment. This would help many people with MLTC to stay healthy and active for longer, without the burden of taking multiple different medications for each condition.
PI: Dr Michael John Keogh
This project brings clinical neuroscience with haematology and immunology to build a transformative new interdisciplinary proposal harnessing key strengths of Newcastle University and spanning NIHR Newcastle BRC themes and interdisciplinary research priority areas. It includes the Dementia, Mental Health and Neurodegeneration Theme and the Musculoskeletal Disease and Inflammation Medicine Theme.
Microglia are the major immune cells of the brain that play a critical role in the progression of neurodegenerative disorders such as Alzheimer’s disease. Studies in mice suggest that microglia are self-renewing, and are not added to by immune cells from the blood (such as monocytes) crossing into the brain. Recently however, some monocytes in the blood have been shown to cross into the brain and convert into microglia, meaning that new microglia are added to by monocytes from blood. These monocytes however carry a mutation in their DNA called a CHIP-mutation, which importantly, are associated with reducing the risk of Alzheimer’s disease. To date, we do not understand whether or how microglia carrying a CHIP-mutation slow neurodegenerative disorders, but this is critical to understand in order to develop new therapeutic approaches.
In this study, three research groups that study dementia, immunology and haematology will work together to determine how CHIP-mutant microglia may slow the progression and development of neurodegeneration. Firstly, the team will harness their expertise by growing the first microglia that carry CHIP-mutations using cells provided by a collaborator. Secondly, they will determine whether and how CHIP-mutant microglia may provide protection to neurons (brain cells). To do this, they will grow the CHIP-mutant microglia with neurons and then expose them to inflammation and injurious proteins that can be seen in the brain with dementia. Using a variety of techniques, they will determine whether CHIP-mutant microglia respond differently and protect neurons against damage compared to control microglia.
If the group can identify whether and how CHIP-mutant microglia protect neurons in the brain, then it will prove that monocytes in the blood carrying mutations can engraft into the brain and slow neurodegeneration for the first time. This would open entirely new treatment opportunities for patients with a variety of neurodegenerative disorders.
PI: Tiago Costa
The team will study depression in people with heart failure, a common co-morbidity with high burden to patients and the NHS, which responds poorly to antidepressants. Novel treatments are badly needed. This project aligns with the aims of the Dementia, Mental Health and Neurodegeneration Theme, Musculoskeletal Disease and Inflammation Medicine Theme and the Digital Health, Ageing Innovation and Inclusion Theme.
The vagus nerve connects the brain with all organs in the body. It influences heart rate, mood and energy levels. In vagus nerve stimulation (VNS), a surgically implanted device stimulates the vagus nerve. This treatment helps people with depression. It also helps people with heart failure to have a better quality of life and to walk further. It doesn’t seem to do this by improving the function of the heart. It may be that it acts by improving mood and fatigue. Many people with heart failure also have depression. Depression worsens fatigue and quality of life. These relationships suggest that the vagus nerve has an important role in linking brain and heart. With transcutaneous auricular VNS (taVNS) the vagus nerve can be stimulated via the skin of the ear, without surgery. This is safe, painless and has potential to help untangle how VNS works.
Our hypothesis is that VNS improves quality of life by improving fatigue and mood. To test this, the group will conduct a study of taVNS in 50 people with heart failure. They primarily want to know if it improves quality of life, while other measures will help explain how it does this. Almost one million people in the UK suffer from heart failure. A quarter of them will also suffer from depression, and struggle significantly more. The findings could therefore help improve the lives of many NHS patients.