NIHRDataInsights/HRCSData huggingface dataset:
Title: Advanced FACS equipment for stem cell research.
Funder: Wellcome Trust

Abstract: The development and maintenance of various organs and tissues in mammals largely depend on populations of immature cell types called stem and precursor cells. These cell types are of significant importance for understanding fundamental biological processes and hold a great hope for developing new treatments in regenerative medicine. The applicants are part of a larger national centre for Regenerative Medicine recently received an MRC Centre for Stem Cell Research award. Their expertise spans acr oss broad areas of stem cell research, from embryonic stem cells, capable of generating all cell types in the animal, to stem and precursor cells supporting individual normal tissues and cancer stem cells. The identification and purification of rare stem cell and precursor populations is a prerequisite for their accurate biological characterization and therapeutic use. Flow cytometry is a pivotal technique used for this purpose, based on the detection of various biological (including genetica lly engineered) molecules using fluorescent reagents. We propose to significantly enhance the biological analysis of stem and precursor cells by using new advanced multi-parameter flow cytometry equipment, which will allow us to conduct considerably more accurate purification and detailed characterisation of behaviour and molecular mechanisms in normal and cancer stem cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM;CANCER AND NEOPLASMS;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Flow Cytometry for the Queen's Medical Research Institute.
Funder: Wellcome Trust

Abstract: The Queen s Medical Research Institute houses over 600 biomedical researchers encompassing inflammatory disease, cardiovascular science and reproductive health. As part of our studies, many of us need to identify rare cell populations in healthy and diseased tissues. We need to separate these cells, for example stem cells that are found within the brain or the liver, or immune cells that can drive unwanted inflammatory responses in autoimmune disease, or allergy. Once we have isolated these cell s we can study their functions, grow them in the laboratory and in some cases test them as a therapy (eg stem cells). The machines that allow us to separate and analyse these cells do so based on colour. Different cells can be identified based on different combinations of colours. Our present machines are very limited, allowing us to discriminate on 4-7 colours. Advances in our science mean we now need to discriminate cells on up to 15 different colours and our research output will be severely i mpeded if we cannot. This grant will allow us to buy the new generation of machines that are essential if our science to remain internationally competitive, leading to improved understanding of disease and to new therapeutic opportunities.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM;CANCER AND NEOPLASMS;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: North West England MRC Fellowships in Clinical Pharmacology and Therapeutics
Funder: Medical Research Council

Abstract: The North West Clinical Pharmacology Training programme utilises the complementary expertise of: the Universities of Liverpool and Manchester building upon strengths in translational research and; Two major pharmaceutical companies (AstraZeneca and GlaxoSmithKline) and 2 contract research organisations (ICON and Medicines Evaluation Unit) to provide a highly integrated !?without walls!? training scheme. The programme is based on an established Liverpool-Manchester collaboration, the MRC Centre for Drug Safety Science, which provides the management framework. It is based around the successful training programme which has been the hallmark of the Department of Pharmacology and Therapeutics in Liverpool, where there is a seamless working relationship between clinical and basic pharmacologists. The focus of the scheme will be on Stratified Medicines and Drug Safety in the clinical areas of Paediatrics, Infectious Diseases and Inflammation and Repair. Over a period of 4 years, we aim to train 12 clinical research training fellows to undertake a doctoral thesis. The fellows. specific skills training will be supplemented with generic and transferable skills training. We will implement a taught clinical pharmacology programme in keeping with the curriculum approved by JRCPTB. Trainees will interact closely with our industrial partners. Industrial placements will be developed in a bespoke manner to suit the individual needs of the trainee and their project aims The key to the programme is its flexibility which will enhance the student experience. A two-stage interview procedure will be implemented to ensure the selection of the best students and the best projects consistent with the recruitment procedures utilised with the MRC. Academic clinical fellows will form the main source for recruits. All trainees will be comprehensively monitored, being supported by their supervisors, an advisory panel and mentor. Annual showcase events will allow fellows to present their work, and interact with other students, and key players from both Universities and external academics. We envisage, and will actively promote, that on completion of the PhD, the trainees will move to lecturer posts. Our partners have contributed 46% of the total cost of the programme which represents significant added value. Our aim is to develop high-calibre clinician scientists of the future with the ability to link bi-directionally between clinical and basic science, from molecule to man, and from bench to bedside. Such individuals will have benefited from research experience in the settings of academia and industry, and could thus function as future research leaders in either sector.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM;INFECTION
Title: Blimp1/PRDM1 functional roles in adult homeostasis.
Funder: Wellcome Trust

Abstract: We want to understand how multiple types of cells within a complex tissue such as the adult intestine communicate to promote self renewal and also execute specialized functions such as uptake of nutrients and immune protection. We are particularly interested in the possible roles played by a key transcription factor Blimp-1/PRDM1, and aim to learn more about how evolutionarily conserved zinc fingers among the most abundant proteins in eukaryotic genomes, have been endowed with the ability to co ntrol global gene expression patterns and consequently shift the developmental programme in so many different cell types.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM;ORAL AND GASTROINTESTINAL
Title: Defining the pathological cellular interactions and developmental features of hidradenitis suppurativa
Funder: Medical Research Council

Abstract: Hidradenitis suppurativa (HS), is a debilitating dermatological condition, causing inflamed nodules primarily in axillae and groin skin. Our understanding of disease pathomechanisms and treatment options remains limited. The studies, thus far, have demonstrated both pilosebaceous distortion and inflammatory infiltrate contributing to disease pathogenesis. However, the precise cellular and molecular mediators underpinning HS pathogenesis are unknown. This study aims to define the pathological cellular interactions and pilosebaceous developmental features present in HS by profiling the cell types, including pilosebaceous units and immune infiltrate, in early HS and determining the cellular and molecular interactions using spatially-resolved and single cell transcriptomics. The findings will be verified in a larger patient cohort by deconvoluting bulk transcriptomics datasets and undertake focused protein-level validation studies using imaging mass cytometry of key cell types and markers. Finally, the gene expression profile in HS will be compared to human prenatal skin and hair follicle-enriched adult skin to determine whether HS pilosebaceous structures are distinct from healthy skin and whether aberrant follicular development occurs in HS. These experiments will provide novel insights into the pathogenic origins of HS and highlight potential new markers that could be therapeutically targetable.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM;SKIN
Title: Predictive modelling of major trauma PROMs using machine learning
Funder: The Health Foundation

Abstract: Every year across England and Wales, 16,000 people die after injury and many tens of thousands are left disabled for life. In the early stages after injury, some patients will have a good chance of recovery while others (for example, those with severe head injuries) will need a higher level of therapy input. However, for a large group of patients in between these extremes, it is difficult to know what the outcome will be. There is already a well-developed system for collecting national data about major trauma patients – the Trauma Audit and Research Network (TARN) – and a more recent system for major trauma Patient Reported Outcome Measures (PROMs). This project from the University of Leicester and partners took major trauma PROMs data to the next stage by linking it to the data held within TARN to create a model to predict PROMs. The research found that, using information available soon after injury, a mathematical model can predict what a patient will say about their health when asked six months later. There is a 70% accuracy for predicting outcomes. This model can potentially be used to audit the quality of care in a hospital by asking ‘Did the hospital achieve the patient outcomes that were predicted?’. Hospitals that perform worse than expected can then be identified and improvement steps taken. The researchers also compared different mathematical methods of making a prediction, which increased understanding of the potential strengths and weaknesses of each method when applied to patient data. The work has provided a new quality measure for national clinical audits, allowed therapists to target interventions, enhanced patient involvement in their recovery and enabled researchers to identify high-risk groups for intervention studies.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;INJURIES AND ACCIDENTS
Title: The children of 'looked after' children: care outcomes and experiences
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Young people who have lived in residential, foster or kinship care are more likely than the general population to become parents at a young age. It is believed that these young parents are also more likely to need support than other parents. Some care-experience parents will be subject to child protection interventions and for some, such interventions will result in their children being taken into care and adopted. The extent of this social problem is unknown and evidence is required on the care outcomes of children of care-experience parents and how be to support these families. This research will review the international evidence on outcomes for the children of care-experienced parents. This will include analysis of patterns and correlations concerned with care-experienced parents, as well as evidience related to interventions designed to support such families. The issues will then be investigated within the Welsh context. This will include the interventions and support currently experienced by this population, together with their associated needs and risks.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: Identifying and responding to child neglect in schools
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Child neglect is possibly the most complex form of child maltreatment to respond to. This is because it is often chronic, rather than based on specific incidents as physical and sexual abuse maybe. It is often difficult to identify in a timely manner whether the care a child is receiving is poor enough to be labelled neglect. It is also usually broad based and has a range of causes. This makes it difficult to provide comprehensive help that will improve the child’s situation sufficiently. Child neglect is the most common form of child maltreatment and when serious the consequences can be severe. The Welsh Government has responded to the need to improve practice by commissioning a Child Neglect Project in conjunction with the voluntary sector. This project has identified the role of schools as being important for identifying and intervening in cases of neglect.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: Developing a Community Singing-Based Intervention for Perinatal Mental Health in The Gambia
Funder: Medical Research Council

Abstract: Perinatal mental health problems affect up to 1 in 5 women worldwide. Stress, anxiety and depression in pregnancy affects not only the mother but can also have long-term adverse effects on her child, via biological mechanisms in utero. Postnatal depression can reduce her ability to provide sensitive and responsive caregiving, and this can also impair child development. Mental health problems in the perinatal period are a particular challenge in low and middle-income countries (LMICs) where they can be at least twice as frequent as in higher income countries. Our geographical context for this work will be The Gambia, West Africa, where mental health services are minimal, services for perinatal mental health are nonexistent and high levels of stigma associated with mental health issues, as well as specific local attitudes and beliefs, impede recognition and prevent help-seeking behaviour.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: Childhood interactions with social services and risk of poor health and social outcomes in adulthood: a population wide data linkage study
Funder: Medical Research Council

Abstract: Aims: To develop the UK's first historical, population-wide cohort of children in contact with social services by linking 30 years' of social services data to three waves of Census returns, prescription medication data and death records to investigate the effect of contact with social services in childhood on adult mental health and social outcomes. Objectives: To first complete advanced training, building upon my existing skills set, to become an expert in the manipulation, management and analysis of large, longitudinal administrative datasets with a focus on life course analytical techniques and Multilevel Modelling. Then secondly, to investigate the effect of contact with social services in childhood on adult mental health and social outcomes via four specific research questions focusing on (1) changes over time, (2) determinants of poor outcomes and variation within families, by reason for entry to care or placement type, (3) critical periods, and (4) generational effects. Methodology: The is an administrative data linkage study utilising 30 years of social services data enhanced via unique linkage to all contemporaneous Census returns, data on medications and death records. Life course epidemiological analysis and Multilevel Modelling techniques will be utilised to tease apart observed associations. Scientific Opportunities: This Fellowship will allow me to build capacity in the manipulation and analysis of large administrative data and to generate new knowledge surrounding the effect of a history in the social care system in childhood on adult social and mental health outcomes. It will also result in the development of a unique data resource for use by other UK researchers in the field.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: Exploring the potential of civic engagement to strengthen mental health systems in Indonesia.
Funder: Medical Research Council

Abstract: The aim of this study is to develop a testable systems level, culturally appropriate civic engagement framework for use in Indonesia to strengthen local mental health services. People with psychosis and their carers will receive training in research methods and will be involved in all stages of the project. Indonesia has the highest rate of years of life lost to disability or early death from Schizophrenia than any other country in the world. More than 90% of people with mental illness do not get any treatment and tens of thousands of people with psychosis are illegally detained ('pasung') in the family home. Civic engagement, a core part of the recent WHO global strategy, has the potential to address some of these challenges through the development of person-centered models of care. This mixed methods study, underpinned by a realist approach, will comprise four phases: Phase 1, a systematic review of peer reviewed studies and grey literature, will identify the range of approaches to civic engagement implemented in South East Asia, and review current evidence around the use of these approaches. Phase 2 will be a social network analysis to map the main sources of collaboration and evidence used by stakeholders when making decisions in mental health services and will identify opportunities for civic engagement. Phase 3 will comprise interviews with key stakeholders across the health system, including, policy makers, clinicians, service users and carers, to explore their views of civic engagement and how it might work for people in Indonesia. In Phase 4 we will hold a series of synthesis workshops with local stakeholders to present our findings and co-produce a testable, culturally appropriate civic engagement framework and implementation strategy. During these workshops observational film and video-interviews will be used to capture important and impactful thoughts and messages amongst stakeholders.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: A machine learning approach to understanding comorbidity between mental and physical health conditions
Funder: Medical Research Council

Abstract: The key aim of the research is to enhance our understanding of the comorbidity between mental and physical health conditions by combining the disciplines of public health, computer science and psychiatry. The objectives of the research are to improve the prediction of the onset of co-morbidities between mental and physical health conditions (such as major depressive disorder and diabetes) and related adverse outcomes (e.g. hospitalisation and mortality). A range of data sources will be used to test the utility of implementing a machine learning approach to prediction. For example, using the UK Biobank and Generation Scotland cohorts will allow the exploration of a range of biological, environmental and lifestyle factors. Linked administrative health data (including the Scottish Morbidity Records, disease registers, Prescribing Information System, mortality records and the census) will facilitate the exploration of patients' complex medical histories and social characteristics (e.g. occupations). Machine learning algorithms (e.g. deep neural networks and random forest) will be used to learn from patterns in a range of big data by splitting the data into training and test datasets, assessing the algorithm performance and comparing the results with other methodological approaches. By identifying factors that are highly predictive of physical and mental health comorbidities and adverse outcomes, there is great potential to develop new approaches to patient stratification and novel precision medicine interventions. Collecting these data within medical settings may facilitate the development of improved diagnostic, treatment and preventative measures in clinical and public health practice.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Title: Neural circuits, instincts, sleep and appetite
Funder: The Francis Crick Institute

Abstract: The overall aim of our research is to understand at the cellular and computational levels how chemical and physical signals inside and outside the body (sights, sounds, nutrients) are detected and processed in the brain to generate normal and pathological behaviour. Our specific focus is on neurons regulating body energy balance. Understanding their function is important because energy balance disorders affect 1 in 3 people world wide, and are a leading cause of morbidities in diabetes and cardiovascular disease. Our research plan involves using a large range of modern tools, including in vivo optical and electrical recordings from specific neurons during free-will eating behaviour, chemogenetics, optogenetics, circuit-mapping electrophysiology, multiphoton and confocal imaging, metabolic screens, and transgenic models (Cre lines, reporter lines). Our specific research objectives are 1) to define when energy-regulating neurons are normally active; 2) to disrupt this activity while measuring energy or behavior end-points, thereby elucidating physiological and pathological importance of specific brain signals. Our experimental are performed predominantly on rodent models, which share energy-control neurons with humans, and well as in reduced brain-slice preparations in vitro. Some of the neurons that we focus on are: orexin/hypocretin neurons, melanin-concentrating-hormone neurons. Agouti-related peptide neurons, GABAergic neurons of the lateral hypothalamus, dopamine neurons and dopamine-receptor neurons. We also carry out computational simulation that aim to understand the overall control logic for body energy balance. We view these currently-elusive general control laws as the ultimate aim of our research, since proper treatment strategies for energy balance disorders cannot arise purely from elucidating a “parts list” of every specific neural and genetic component of the control system.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH