Find out about the winners of the 2021 grant round and their projects by clicking through the tabs below.
Dawkins & Strutt grant to assist research in the field of gastroenterology
Dr Isioma Egbuniwe
Targeting bile duct tumour – immune crosstalk for improved
Cholangiocarcinoma (CCA) is the second most common type of liver cancer and arises from a malignant transformation of cells lining the bile ducts within and outside the liver. The development of CCA remains poorly understood, with sub-optimal outcomes for patients diagnosed with this disease. Despite CCA tumours being known to have a significant immune component within the tumour microenvironment (TME), immunotherapeutic treatment strategies have been trialled with relatively disappointing results. An improved understanding of the mechanisms underlying immune cell responses within the CCA TME is therefore urgently needed.
Using a combination of novel 3-dimensional tumour culture systems, as well as digital pathology and computational analyses, we aim to investigate biological cooperation via transcriptional signalling between bile duct epithelial cells and immune cells within the CCA microenvironment. Our findings could potentially lead to the discovery of new therapeutic targets and/or prognostic tools for use in the management of patients with CCA.
Doris Hillier grant to assist research into rheumatism and arthiritis
Dr Anushka Soni
Moving Towards A Stratified Medicine Approach In Fibromyalgia
Fibromyalgia is a common condition affecting 1-5% of the UK population. It causes chronic widespread pain and other debilitating symptoms including sleep and mood disturbance, fatigue, and trouble with thinking and concentrating.
We don’t fully understand what causes fibromyalgia, but brain imaging studies show that pain processing is different from healthy volunteers. There are no specific tests to diagnose fibromyalgia, so a very mixed group of people, with symptoms of widely differing severity and disability, are given the same diagnosis.
Although exercise is currently the mainstay of first line therapy, it does not significantly improve many symptoms including fatigue, sleep disturbance, mood and cognitive disturbance. Current guidelines acknowledge that a one-size-fits-all approach is likely to fail and highlight the need for a tailored solution.
My project will focus on developing a tool to identify subgroups of patients. I will apply machine learning methods, which use statistics to find patterns in data, from two datasets: UK Biobank (a large scale biomedical database), and a hospital-based study of patients with fibromyalgia.
Patients living with fibromyalgia have reviewed the project and will continue to advise throughout the project. They will help to interpret and share the results with the wider community.
H C Roscoe grant to assist research into the elimination of the common cold and/or other viral diseases of the human respiratory system
Professor Peter Stockley, BSc, PhD
University of Leeds
Professor Reidun Twarock MSc, PhD
University of York
Validating and targeting the primary assembly regulation system in HRV
Infection by picornavirus, such as the Human Rhinovirus (HRV), depends on prior assembly of a precise molecular machine – the virion. We have shown for a number of viral pathogens that such assembly relies on multiple, dispersed, packaging signals that are recognised by viral capsid protein. These act collectively to promote efficient virion assembly. In picornaviruses, these genome-encoded regulatory elements occur in the form of stem-loop structures harbouring triplet purine-rich recognition motifs.
Using SELEX and bioinformatics, we previously characterised the molecular details of the packaging signals in enterovirus-E/F and poliovirus, two viruses in the same family as HRV. Our recent work suggests that the molecular characteristics of these packaging signals are shared across the family, i.e. that similar motifs also occur in rhinoviruses, including the C strain implicated in exacerbating asthmatic conditions. In order to exploit this discovery for therapy, identification of PS motifs by themselves is not sufficient.
In our HC Roscoe supported research programme, we will characterise the collective action of the PS ensemble, and thus identify key players as potential drug targets, and their mode(s) of action. This will lay the foundation for a two-pronged therapeutic approach targeting both the gRNA and protein partners forming these PS-CP interactions.
Helen H Lawson grant to assist paediatric research
Dr Katherine Atkinson MBChB (Hons), MSc (Distinction), MRCPCH
Wolverhampton New Cross Hospital
A Novel Method to Track Epigenetic Transmission at the Start of Development: Super-Resolution Chromosome Imaging During Asymmetric Cell Division
Amazingly, despite differences in appearance and function, all cells in the human body contain the same genetic information. The differences between cell types are due to differences in which genes are switched on or off. The processes involved in regulating and remembering these patterns of gene expression as cells grow and divide are referred to as epigenetic.
Cells generally retain their identity when they divide (mitosis). But sometimes it is necessary to change identity. This is most notable during development of the foetus but also occurs in maintenance and repair of mature tissues.
To change identity, cells undergo asymmetric mitosis, where one daughter cell retains its original identity while the other adopts a new identity. My project aims to elucidate the incompletely understood epigenetic processes that mediate this change.
I will use a novel microscopical approach that will allow me to scrutinize asymmetric cell division at the single-cell level. I will focus on the possible role of DNA-associated proteins, the histones, and their information carrying modifications, known to be key players in epigenetic processes.
This will enable me to explore how histones contribute to epigenetic memory in early development and address the question of whether epigenetic disruption at this early stage might predispose to disease in later life.
Dr Emily Bowen BSc, MBBS, MRCP, PhD
University of Bristol
Determining the role of VEGF-A in the development of Shiga toxin associated Haemolytic Uraemic Syndrome.
Infection-associated haemolytic uraemic syndrome (HUS) represents a major public health issue as it is caused by infection with Escherichia coli (E.coli) entering the food chain. Infection-associated HUS is the commonest cause of kidney failure in children, with 1 in 20 children dying.
Currently, there are no specific treatments available for the condition. Early work suggests that following infection with E.coli, interaction between specialised cells in the kidney are responsible for over-activity of the immune system.
Our work has identified that a local reduction in the signalling protein VEGF-A (vascular endothelial growth factor A) occurs in Shiga toxin HUS. I will be investigating how this leads to the development of the disease using human kidney cell models and culture of 3D glomerular spheroids.
This project will provide new insights into the mechanisms underlying Shiga toxin HUS and has great promise to lead to novel therapeutic targets to help treat paediatric patients with this devastating condition.
Josephine Landsell grant to assist research into heart disease
Dr Tian Zhao MA, MBBS, MRCP, MPhil, PhD
University of Cambridge
The effect of low-dose interleukin-2 on human atherosclerotic plaque immune cells at single cell resolution.
Chest tightness during exertion (angina), heart attack, and stroke cause long-term disability and death for millions of patients worldwide every year. These conditions are caused by the narrowing of the blood vessels, known as atherosclerosis. This process is a result of fat build-up in the blood vessel wall and the immune system's long-term overactivation, also called inflammation. Frustratingly, despite knowing all this, no medicines are currently available to reduce inflammation in the blood vessels.
In our previous clinical trial, we adapted the use of an existing medication (aldesleukin) to treat, for the first time, patients with a recent heart attack to reduce inflammation. To help us further develop this concept, we next need to find out if aldesleukin is also decreasing inflammation in the narrowed blood vessels themselves. To achieve this, we plan to recruit patients already scheduled to have a narrowing in their neck blood vessel surgically removed. We will treat half of these patients before their surgery with aldesleukin. At the time of surgery, we will take the atherosclerosis and examine it using state-of-the-art techniques (single-cell RNA sequencing) to see if aldesleukin is having the desired effects of reducing inflammation and disease progression.
J Moulton grant to assist research into mental health through clinical trials
Professor Christina Van der Feltz-Cornelis MD, PhD
University of York
Effect of Adalimumab in Conversion Disorder/Functional Neurological Disorder (CD/FND). Randomised clinical trial. (CANDO1)
Conversion disorder/functional neurological disorder(CD/FND) is a condition that has been known in psychiatry and neurology for a long time, but that is only partly understood. People with CD/FND present with symptoms that seem neurological, but that cannot be explained by a neurological condition. Currently there is a lack of evidence-based treatment, patients can become severely disabled, and there is a high clinically unmet need.
New research in blood samples of patients with CD/FND showed elevated inflammatory proteins, so-called cytokines, such as Tumor Necrosis Factor-alpha (TNF-a). It also showed elevated small proteins called microRNA that influence the expression of genes in the cell. If this plays a role in the occurrence of CD/FND, treatment with Adalimumab, a TNFa inhibitor, might help improve the symptoms.
This project aims to explore the effect of Adalimumab on symptom improvement in patients with CD/FND with elevated cytokine levels in a Randomised Clinical Trial. We will also explore if any clinical improvement is associated with the improvement of cytokine and microRNA levels.
The findings of this study will inform a placebo-controlled trial, which could potentially improve the outlook and prognosis for people with CD/FND.
J Moulton grant to assist research into stroke
Professor Holly Bridge BA (Oxon), MSc (Edin), DPhil (Oxon)
University of Oxford
Rehabilitating visual deficits caused by stroke.
Holly Bridge is a Professor of Neuroscience based in the Wellcome Centre for Integrative Neuroimaging, University of Oxford.
Her research project aims to determine the neural effects of a visual rehabilitation programme for people who have suffered a stroke to the occipital lobe leading to hemianopia. Hemianopia, the loss of vision on one side of space, usually results from damage to the first cortical brain region to receive information from the eye (primary visual cortex). Even when this area is damaged, some patients are able to detect visual information, particularly if it is moving or very salient. By using a 6-month visual training programme the project aims to increase this residual vision through strengthening visual pathways that avoid the primary visual cortex.
Using magnetic resonance imaging (MRI) before and after training, we will investigate the changes that occur in the visual areas of the brain, in terms of structure, function and connection strength and relate to the improvement in vision due to training. Understanding the brain regions that are critical for successful visual rehabilitation will guide future training programmes and facilitate targeting of those patients most likely to improve visual function.
The James Trust grant for research into asthma
Dr Hugo Farne BMBCh MRCP PhD
Imperial College London
Early antiviral responses to human rhinovirus challenge.
The bulk of the morbidity and mortality related to asthma is during periods of acutely increased symptomatology called ‘exacerbations.’ Roughly half of asthma sufferers experience such an exacerbation each year. Most of these events are triggered by viral infections, usually the common cold virus (rhinovirus).
A key part of the body’s defence against viral infections is to produce antiviral proteins called ‘interferons,’ which have a myriad of effects to stop viruses. Previous work on cells taken from volunteers with asthma and healthy controls and infected with rhinovirus in the lab suggests interferon production is impaired in asthma. However, when human volunteers with asthma are infected with rhinovirus, high levels of interferon are found a few days later – along with high numbers of virus. Whether the high virus numbers are the result of an initially weak interferon response, with subsequently unchecked viral replication leading to exaggerated interferon levels, is unknown as no one has measured interferons early in infection.
By infecting volunteers with asthma and healthy controls with rhinovirus at a known time, only done in a handful of centres worldwide, I will be able to measure interferons within hours of infection and well before symptoms develop. Interferon treatments are available and so insights from this work could directly affect clinical drug development in asthma and potentially other diseases where interferon production is thought to be abnormal, including COVID.
Kathleen Harper to assist research into antimicrobials
Dr Monique Andersson and Dr Susanne Hodgson
Oxford University Hospitals NHS Foundation Trust
Improving Outcomes in Necrotising Otitis Externa (IONOE)
Necrotising otitis externa (NOE) is an invasive infection of the external ear canal. It typically occurs in the elderly, diabetic or immunocompromised patients. The disease is associated with notable mortality. The severe ear pain and hearing loss can have a profound effect on the quality of life and independence of patients. Treatment involves prolonged courses of broad-spectrum antibiotics, often intravenous, necessitating considerable inpatient stays with the attendant risks of long-term venous access.
No established national or international treatment guidelines exist for NOE and published data is limited. In particular, the optimal choice, route and administration and duration of antibiotics remains uncertain. A recent publication has suggested wide variability across the UK.
We have initiated the formation of the UK NOE Collaborative: a multi-disciplinary working group of clinicians (ENT, radiology, infection) to establish a multi-centre, prospective study of NOE. The primary objective will be to describe the demographics, clinical presentation, management, in particular the antibiotic choice, route and duration, and outcomes of these cases.
This data will inform high-quality clinical trials to optimise the antibiotic treatment of NOE, ultimately minimising the profound effect of this disease on the quality of life of patients.
Margaret Temple grant to assist research into schizophrenia
Dr James Bisby BSc, MSc, PhD & Dr Michael Bloomfield
University College London
The role of aberrant memory processing in psychosis: an fMRI study.
Schizophrenia is a leading global cause of morbidity and mortality. Experiencing developmental psychological trauma, such as physical, sexual, emotional abuse and neglect in childhood and adolescence, increases the risk of psychosis and contributes to approximately a third of all cases of psychosis.
We currently lack an understanding of how developmental trauma increases vulnerability to psychosis and there is a lack of evidence-based treatments for adult survivors of developmental trauma with psychosis. Traumatic experiences can severely impact memory processing, both at the time of the trauma and in its aftermath, leaving memories fragmented and disorganised. There is also evidence that vulnerability to psychosis is related to a disruption in how our brains process memories of events.
This project aims to investigate memory processing in adults who have experienced childhood trauma by looking at whether higher levels of memory fragmentation and disorganisation is related to psychotic symptoms and predicts a vulnerability for psychosis. We will also use functional neuroimaging to examine alterations in brain areas supporting memory and how this might contribute to an increased risk of psychosis. This approach will have the potential to impact people who have experienced psychological trauma by helping to identify risk factors for psychosis, and by informing the development of therapeutic approaches aimed at improving symptoms.
Scholarship Grant to assist research into the mental health of medical students
Dr Judith Johnson BSc, ClinPsyD, PhD
University of Leeds
& Dr William Lea
University of York
REBOOT: An Evaluation of a Supportive Intervention in Medical Students
One in two medical students report high burnout and one in three experience elevated depression. Many stressful experiences for medical students occur on placement, including exposure to dying patients and death; fear over making medical errors and involvement in errors and dilemmas concerning decisions about patient care.
Placement-related stress has been further increased by the COVID-19 pandemic, but no intervention currently exists to prepare and support medical students with placement-related stressors.
Our study will address this gap by adapting and evaluating REBOOT (Recovery-BOOsting Training), a coaching intervention which has been linked with increased confidence and resilience in multidisciplinary healthcare professionals and students. Phase 1 will conduct focus groups with medical students, newly qualified doctors and medical educators to explore how REBOOT should be adapted for medical students.
Phase 2 will evaluate the adapted REBOOT intervention with medical students, assessing whether it improves confidence, depression, burnout and psychological resilience. It will also be assessed via qualitative interviews, which will explore participants’ experiences of the intervention in more depth.
Vera Down grant to assist research into neurological disorders
Dr Ruth Dobson MRCP, PhD
Queen Mary University London
Dr Emma Tallantyre BMBS, PhD, FRCP
Cloning neuropathy-related human monoclonal antibodies to develop precision immunotherapies
There are now a number of disease modifying therapies available to treat multiple sclerosis (MS). Many of these act on the immune system, and cause immunosuppression. Concerns about whether and how these treatments affect the effectiveness of vaccines have caused major concerns during the COVID-19 pandemic. Both clinicians and people with MS need more information about this, so that treatments can potentially be tailored to ensure safety along with clinical efficacy.
This project will study the nature and duration of immune response to COVID vaccination in people with MS taking anti-CD20 monoclonal antibodies (which are given every 6 months, and specifically target antibody producing cells), treatments that supress a broad range of immune cells, and people not taking any MS treatments. We will build on work that we have been doing throughout 2021, where we have looked at the antibody response to the initial vaccine course in people with MS. As a result of this grant, this work will be extended to look at the T cell response, along with the antibody response to booster vaccinations. We will focus on looking at the impact of the timing of vaccination with respect to immune cell depletion, and the relationship between initial antibody response to vaccination and response to booster vaccination.
This research will directly inform the timing of treatments and vaccination in patients with MS and other neuroinflammatory disorders, and provide data informing clinicians how to assess vaccine response in these individuals. It will inform patients and clinicians about some of the benefits and risks of switching, suspending or delaying treatment in order to optimise vaccine response.
BMA Foundation Awards Ceremony 2020
BMA Foundation for Medical Research
For more information, please get in touch:
Corporate development, British Medical Association, Tavistock Square, London, WC1H 9JP
Tel: 0207 383 6341
Email the team: email@example.com