NIHRDataInsights/HRCSData huggingface dataset:
Title: Environmental Impact Assessment of Biobanking Strategies: Creating a Sustainable Biobanking Roadmap for sample storage
Funder: Medical Research Council

Abstract: The UK has made a commitment to achieve net-zero by 2050. To achieve this, the UK must develop environmentally sustainable health research strategies immediately, including biobanks. While biobanks support a wide range of health researchers who access their resource, they are also associated with unintended environmental impacts, including those associated with natural resource extraction and consumption, carbon emissions, waste, the production of hazardous chemicals, and impact of biodiversity. This project focuses on their impacts associated with carbon emissions. A primary source of a biobank's emissions comes from the storing of tissue and other biosamples at ultra-low temperatures. This project aims to assess the carbon emissions associated with two ultra-low temperature storage options for biobanks: ultra-low temperature (ULT) freezers and liquid nitrogen (LN2). Using a case study approach of three biobanking sites, this project will assess both the direct and embodied carbon emissions. It will also consider how different storage configurations affect these assessments, including decentralised versus centralised ULT freezer storage, and generating LN2 on-site versus having it delivered. Finally, it will assess the accompanying financial costs for each storage approach and configuration. These assessments will be drawn together in two stakeholder workshops that will explore the perceived drivers and barriers associated with each storage strategy (financial, social, political etc), including what pressures exist for individual researchers to choose a particular option as opposed to another. As much as possible they will also discuss the inter-relationship between carbon emissions and other environmental impacts, and any trade-offs between them. Findings will be co-designed into guidelines on how institutions and funders can best support researchers who biobank samples attain the most environmentally sustainable practices.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Developing frameworks for eco-directed sustainable prescribing: Towards reducing environmental pollution from healthcare practices
Funder: Medical Research Council

Abstract: The prescription of a medicine is the most common intervention in healthcare - but this activity negatively impacts the environment, and pharmaceutical pollution is now a well-recognised global public health and environmental issue. Healthcare sustainability targets call for improvements to prescribing and medicine selection, as current practices are unsustainable. Improving medicine selection and use can reduce pharmaceutical pollution from healthcare. This project will develop and evaluate an eco-directed prescription framework that incorporates environmental sustainability with clinical and cost effectiveness. This proposes that if pharmaceuticals are of comparable medical efficacy, safety, and effectiveness, then the environmental impact (e.g., drug ecotoxicity, predominance towards AMR) should be considered during the formulary process to better inform prescribers, enabling them to make more sustainable prescribing choices. The research investigators will: interrogate environmental and prescribing data; evaluate ecotoxicological data and drug physicochemical properties to develop environmental hazard indicators; prioritise criteria through structured consensus and focus group activity; develop a robust decision-making formulary framework through novel application of Bayesian Belief Network modelling; and, engage with patients, practitioners, and prescribers to assess suitability. The investigators will work with project partners and networks/stakeholder groups to disseminate, educate, and develop post project activity for a pilot trial towards implementation. This project will meet the opportunities and challenges of this call, whilst also: enhancing research sustainability and generating innovation; integrating cross-sector research methods; ensuring genuine PPI and cross-sector stakeholder engagement; supporting high-level research impact within and beyond the environment-healthcare sectors; and addressing environmental pollution from healthcare practices.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: GoGREEN: REDUCING THE ENVIRONMENTAL IMPACT OF OPERATING THEATRES - A BEHAVIOURAL SCIENCE APPROACH
Funder: Medical Research Council

Abstract: NHS contributes substantially to the UK's carbon footprint. Operating theatres (OTs) are shown to be three to six times more energy-intensive than the rest of the hospital and a major contributor of waste. Pro-environmental initiatives have proposed practical guidelines to minimise environmental impact in OTs such as reduction of anaesthetic gas, rationalising surgical instruments and opting for reusable products. However, many of the proposed environmental solutions overlook the behavioural factors that are crucial in the implementation process. This is evidenced in the low adoption of these and similar green surgery guidelines in practice. The aim of this project is to empower theatre staff in the UK to reduce the environmental impact of surgery practices whilst ensuring patient safety. The work will be realised through three work packages in collaboration with Imperial NHS Trust hospitals, Centre for Sustainable Healthcare, Royal College of Surgeons and Imperial's Institute for Global Health Innovation, across one year, addressing the following objectives: 1. to establish evidence-based guidelines for green surgery by systematically reviewing current literature and guidelines for sustainable healthcare and green surgery. 2. to identify the barriers to and facilitators of implementing green surgery guidelines through a combination of survey (in the UK) and in-depth interviews with surgery stakeholders at Imperial Trust hospitals. 3. to co-design interventions for pro-environmental behaviour in the operating theatre or within the surgical pathway with stakeholders through iterative design workshops. Guided by a participatory design approach, the project will use the Behaviour Change Wheel process (Michie et al., 2011), which includes the Capability Opportunity Motivation - Behaviour model (COM-B). This will enable an understanding of the underlying individual, social and contextual factors driving the targeted pro-environmental behaviours.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Environmental Life Cycle Assessment (LCA) of research laboratory protocols
Funder: Medical Research Council

Abstract: We will calibrate the environmental impact profiles of laboratory medical research protocols at ICR. The insights gained will be used by the scientist and environmental analysis teams to co-create re-designs and adaptations to maximise scientific benefit at improved environmental impact, particularly zero carbon. A whole a life cycle (cradle-to-grave) approach, using Life Cycle Assessment (LCA) methodology (ISO 14040/44, EC-PEF), will be applied to up to 5 current ICR laboratory science protocols. This LCA research will create new, detailed, bespoke Life Cycle Inventory (LCI) datasets for all materials, chemicals, energy, wastes (incl. recycling) and equipment and staff time needed per protocol to establish robust baseline environmental 'footprints'. These LCA footprints will calibrate the protocols' Global Warming potential (Carbon footprint), resource depletion, ecotoxicity, acidification, eutrophication and other environmental impacts. The 'baseline' LCAs will then be used inform the co-design of revised protocols with equal/enhanced efficiency and accuracy but with calibrated environmental benefits. Examples of at least 2 of these 'environmentally adapted' (EA) protocols will be demonstrated at ICR during the project. The protocols will be selected from the following: Electrophoresis and Blotting, Microscopy and Imaging, Enzyme reactions, DNA and Gene expression analysis, Cell culture manipulations, cell health (viability) and phenotypic assays based on their: i) Frequency of use, ii) Estimated carbon/environmental savings potential, and iii) Potential for miniaturisation and new technology. Initial 'targets' are: Enzyme assays [generic ATP turnover], and Cell viability assays [metabolism based readout]. Assay quality (robustness, reproducibility) is readily quantified (Z prime) to show the EA protocols have no effect on data output. The protocol groups require a diverse range of inputs, operating needs (inc. PPE) and wastes and are in widespread use.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Health Data Research UK - CORE Funds
Funder: Medical Research Council

Abstract: This work is funded by the UKRI Medical Research Council, UKRI Engineering and Physical Sciences Research Council, UKRI Economic and Social Research Council, National Institute for Health Research (England), Chief Scientist Office (Scottish Government), Health and Care Research Wales, Public Health Agency (Northern Ireland), British Heart Foundation and The Wellcome Trust HDR UK - are the UK's national institute for health data science. We are uniting the UK’s health data to enable discoveries that improve people’s lives. Our vision is that every health and care interaction and research endeavour will be enhanced by access to large scale data and advanced analytics. https://www.hdruk.ac.uk/ This funding supports a number of data science initiatives but the following are the high level projects HDR-8001 - HDR UK central infrastructure activities - led by Mr David Seymour HDR-8002 - HDR UK central PPPEI activities - led by Dr Amanda White HDR-8003 - HDR UK central training activities - led by Dr Sarah Cadman HDR-9001 - HDR UK Site Project - Applied Analytics - led by Professor Chris Holmes HDR-9002 - HDR UK Site Project - Better Care - Professor Simon Ball HDR-9003 - HDR UK Site Project - Human Phenome - Professor Harry Hemingway HDR-9004 - HDR UK Site Project - Understanding Causes of Disease - Professor John Danesh HDR-9005 - HDR UK Site Project - Clinical Trials - Professor Martin Landray HDR-9006 - HDR UK Site Project - Improving Public Health - led by Professor Ronan Lyons


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: National Mouse Genetics Network - NMGN - Directors flexible funding award
Funder: Medical Research Council

Abstract: The Network, led by National Director Professor Owen Sansom, will capitalise on the UK’s international excellence in mouse and human genetics, and the wider biomedical sciences. The Network will consist of multiple disease-focused clusters pursuing distinctive, but complementary, challenge-led research and the Mary Lyon Centre at MRC Harwell acting as a central hub generating and robustly phenotyping strains, performing pre-clinical trials, and providing training. Key within these clusters will be both experts in developing mouse genetic models, and translational and clinical scientists to provide a clear path to clinical translation. Furthermore, the clusters will interact with each other to capitalise on the numerous opportunities there will be for cross-disease learning. https://nmgn.mrc.ukri.org/ The award to the NMGN Director includes a ‘flexible component’ allowing the Director to support promising additional activities within the Network (for example, to support existing or new clusters, additional model development, training and networking events). Examples include Somatosensation and Pain – led by Professor John Wood at UCL Horizon Scanning Technology – led by Dr Ben Davies at the Francis Crick Institute


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Authentication of primate pluripotent stem cells for chimaera formation
Funder: Medical Research Council

Abstract: Pluripotent stem cells (PSC) hold the potential to produce unlimited amounts of every cell type of the body. They offer a future vision of regenerative medicine in which damaged or diseased tissues and organs could readily be replaced. To realise this vision it will be necessary to control completely the differentiation of PSC in order to generate safe and fully functional cells and organs. Major efforts are directed at making differentiated products in the research laboratory with protocols that could be converted into clinical manufacturing processes. Despite considerable progress, substantial challenges remain in terms of consistency, maturation to post-natal fully functional phenotypes, scalability, and organ formation. A complementary concept is to harness the force of ontogeny for formation of human cells, tissues and organs in chimaeric animals. In this project we bring together complementary world-leading expertise and resources from the UK and Japan to address this ambitious challenge. The Japanese team have pioneered the chimaera approach, demonstrating inter-species chimaera formation and organ complementation in rodents. They have also created organ-deficient pigs by genetic modification and demonstrated organ generation by blastocyst complementation. Pigs are preferred hosts because they are similar in size and physiology to human, have a large litter size, and are amenable to embryo manipulation and genome engineering. The critical unresolved challenge is to develop suitable human PSC for colonisation of the pig embryo. The UK team are field leaders in the biology of pluripotency and have derived and qualified human naïve PSC. Here the two teams will work together and draw on specialist primate facilities in Japan in order to clarify the capacity and specific requirements for non-human primate PSC to form chimaeras within the same or closely-related species. These investigations will provide criteria for chimaera-competent human PSC, which we will then test for ability to contribute to organ development in pig embryos.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Early Life Exposures And Development Of Non-communicable Diseases In Adolescence: The Drakenstein Child Health Study
Funder: Medical Research Council

Abstract: Non-communicable diseases (NCDs) are increasing globally, with a disproportionate burden in low- and middle-income countries (LMICs), where more than three quarters of global NCD deaths occur. Further, in LMICs, NCDs occur at an earlier age and with greater severity than in high-income countries. Adolescence is a key developmental period during which NCD phenotypes emerge, and specific behaviours or exposures may promote or prevent disease development. However, despite the high prevalence and severity of NCDs and many harmful environmental exposures, there are very limited data on NCD phenotypes or determinants in adolescents in LMICs. This proposal builds on our work in the Drakenstein Child Health Study (DCHS), a birth cohort of 1000 exceptionally well phenotyped South African children who have been followed from antenatal period through age 8 years, including longitudinal assessment of symptoms, growth, adiposity, lung function, neurocognitive development and mental health measures, linked with a comprehensive collection of early life exposures, and very high retention (90%). We will extend the follow-up in DCHS through the critical period into adolescence (age 15years) with detailed phenotyping, measurements of relevant exposures and collection of biological material for research. We will apply FAIR (Findability, Accessibility, Interoperability, Reusability) guiding principles for data management and stewardship to enable efficient and error-free data analysis and increase reusability. Phenotypic data and linked samples in a biorepository will form an invaluable resource for research globally on adolescent NCDs (respiratory, cardio-vascular, mental health). FAIRified data assets will ensure wide global use and optimise potential impact. The overall vision is to identify modifiable risk factors and inform development of intervention strategies to reduce the risk of NCDs and prevent morbidity and premature death in African populations, an area of critical need.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: GroundsWell: Community-engaged and Data-informed Systems Transformation of Urban Green and Blue Space for Population Health
Funder: Medical Research Council

Abstract: Urban environments are powerful contexts that influence lifelong health and wellbeing. They are not consistently nor equitably beneficial for communities, driving social inequalities in non-communicable disease (NCD). Our interdisciplinary researchers, collaborating with stakeholders and citizens, will use urban green/blue spaces (UGBS) as an exemplar to optimise innovative systems-based approaches that work with, and for, communities at high risk of NCD. We will transform systems and community approaches to create urban environments optimising health and co-benefits, while reducing inequalities. Initiating a step change in inclusive research and policy, we work towards the democratisation of research and evidence use. Communities as partners will enable delivery of optimal solutions to inform and innovate action on health inequalities and NCD prevention. Whole system mechanisms of action will be determined through interconnected work packages: 1) co-developing a systems-oriented framework of how UGBS impacts NCD; 2) agent-based modelling to simulate complex adaptive systems to explore how UGBS transformations will reduce inequalities; 3) working with communities and stakeholders to co-develop and evaluate local UGBS interventions using citizen science approaches; 4) curating a shared data repository with UGBS features valued by policy and communities, developing health and NCD indicators at multiple scales to inform and evaluate UGBS interventions; 5) generating evidence on economic impacts of UGBS interventions; 6) identifying pragmatic, systems-level actions to improve policy- and decision-making for equity and sustainability; 7) implementing a stakeholder-informed impact strategy. Our cross-cutting health inequalities theme will embed the consideration of inequalities throughout GroundsWell. Groundswell will be shaped and developed in 3 pioneer cities (Belfast, Edinburgh, Liverpool), with embedded translational mechanisms to ensure UK-wide and global reach.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: The p97/VCP system in Ionising Radiation Response
Funder: Medical Research Council

Abstract: The highly conserved AAA+ ATPase p97 converts its ATPase-driven chemical energy into mechanical force to segregate proteins labelled with ubiquitin (Ub) and/or SUMO from various macromolecules or cellular locations, including chromatin. During this process, p97 turns highly folded substrates into linearised polypeptides that are either presented for proteasome-dependent degradation or recycled. Thus, p97 controls two cellular processes, namely protein homeostasis and DNA repair/genome stability, that are ultimately essential for cellular survival. There are several thousands of p97 substrates and the specificity of p97 towards its substrates is tightly regulated through about 40 known p97 cofactors (cofactors). By forming unknown number of p97 complexes and sub-complexes (p97 with a combination of different cofactors), the cofactors specifically bridge p97 with designated and mostly ubiquitinated and/or SUMOylated substrates. Besides its well-known "unfoldase/segregase" function, p97 can also serve as a platform for substrate processivity, as it co-assembles several E3-Ub ligases, deubiquitinating enzymes or the SPRTN protease that additionally regulate the fate of various substrates. The p97 system is highly relevant for cancer cells as these are constantly on the verge of suffering from lethal effect of proteotoxic stress and an unstable genome. Indeed, numerous reports have shown that p97 overexpression correlates with poor prognosis of various cancer types. The overarching goal of my work is to address the p97 system and its role in proteostasis and genome stability in response to IR. This question is important if we want to understand and explore how the inactivation of the p97 system and consequently induction of both proteotoxic stress and inactivation of DNA repair could potentially cure cancer.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Chromosome Breaks and the DNA Damage Response in Transcribed Genes
Funder: Medical Research Council

Abstract: DNA double-strand breaks (DSBs) can arise through normal DNA metabolism or through exposure to DNA damaging agents such as ionizing radiation (IR). These lesions have the potential to lead to cell death if unrepaired or to chromosomal rearrangements and tumorigenesis if incorrectly repaired. DSBs are normally repaired by one of two pathways termed non-homologous end joining (NHEJ), or homologous recombination (HR) repair. While considerable advances have been made in our understanding of DSB repair, how it occurs in the context of transcription is unclear. The aim of the proposed research is to understand how cells respond to chromosome breaks within transcribed genes to facilitate their accurate repair by homologous recombination. In particular, we will explore the roles of chromatin and the transcription elongation machinery in coordinating DSB detection and HR repair within transcribed genes, and how defects in these processes can be exploited to target particular cancers. We anticipate that these studies will provide new insights into the relationship between transcription elongation and HR repair, and how genome stability is maintained in response to DSBs within transcribed regions of the genome.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE