NIHRDataInsights/HRCSData huggingface dataset:
Title: Imaging dynamics in biophysical/biochemical processes across the hierarchical scales (BioPro Network)
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Biological organs constantly undergo a hierarchical and dynamical set of structural, biochemical and biomechanical alterations which are critical to tissue functioning and growth and whose dysfunction, at multiple scales, is associated with pathologies. These range from individual protein molecules, their self-assembly into and mechanical response as fibres, cellular response to external fields, flows and forces and whole-tissue deformation under physiological loads. The integrative knowledge of these processes - and understanding how they affect tissue and organ function - is a grand challenge in bioengineering and medicine. We will build a network to utilize the latest advances in high resolution, high energy physical-science methods at central facilities which can probe complex matter at multiple scales - including X-ray tomography, X-ray scattering, cryo-EM and light-sheet imaging - to address this challenge. Specifically, we will adapt these techniques to the challenges of working with biological matter in a time-resolved manner - mimicking and modelling the physiological environment during testing, maintaining the tissues in a viable state, correlating information from multiple techniques, minimizing radiation exposure, optimizing signal analysis techniques. Using musculoskeletal degeneration (as in osteoarthritis) as an exemplar, we will enable proof-of-principle projects in these areas via pump-priming funding of multidisciplinary teams, enable researcher exchanges and target early-career researchers in learning these new methods. Via sandpits, workshops, and conferences we will develop, disseminate and document new protocols and techniques for biological process imaging in a quantitative and realistic manner. Our network will seed the development of next-generation techniques that exploit the multiscale capacity and high resolution of new imaging and spectroscopic methods, translating them to the laboratory and clinic.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: QUantifying the Impact of Chronic pain on engagement in paid worK (QUICK)
Funder: Medical Research Council

Abstract: We will develop an instrument to assess the impacts of chronic pain on work ability. It will take account of the range of ways in which people now engage in paid work and the different impacts chronic pain may have: the quantity and quality of work, measures adopted in mitigation, and changes in employment. Specific objectives are to: - identify what instruments have been developed to measure impacts of chronic pain on work, or could be suitable for such (workpackage 1). We will undertake a systematic review of the literature to identify existing instruments that have been used to measure impacts of chronic pain on whether and how people work, or have been used to measure these in other long-term conditions. - determine the key functional impacts of chronic pain on work and to map impacts of pain on work to existing instruments identified above (workpackage 2). We will undertake a narrative synthesis of qualitative literature; focus groups with patients, employers and policy makers; mapping impacts of chronic pain on work to existing instruments and establishing an initial item set to be included in an instrument. These two workpackages will then inform the development of the instrument. This will involve a multi-stage Delphi study involving key stakeholders and the output from this will be a prototype instrument for testing. We will then: - evaluate the performance of the newly-developed instrument. This will include: acceptability, feasibility, comprehension, readability, responder burden, test-retest reliability, and convergent validity with other measures, amongst individuals with chronic pain and in different types of work, and thereby to agree a finalised instrument (workpackage 3) The output from this work will be a new instrument which allows the quantification of the impact of chronic pain (with possible use in other chronic diseases) on work ability, and to more widely identify the life-course impact on work trajectory.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: I AM PHYSIO: Intelligent Assessment of Movement function for PHYSIOtherapy self-management
Funder: Medical Research Council

Abstract: The secondment will focus on developing intelligent video-based tools that will measure movements of patients undergoing physiotherapy exercises and support the clinician to complete assessments remotely. The secondee has expertise in motion capture methods and data analysis of movement data for inferring health status. The host organisation has developed novel physiotherapy triaging tools using artificial intelligence and machine learning methods. The secondment project will focus on developing video-based assessment of movement function. This will be achieved through a combination of new motion capture data led by the secondee, online public datasets and new data captured from the current app userbase. A generative modelling approach will be used to assess functional movement from pose estimates extracted from video data. The resulting solution will provide physiotherapists with the next-generation of tools to support assessments when working on remote video call platforms.


Research activity codes: 5.7 PHYSICAL
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: Understanding the role of immune cells in extracellular matrix homeostasis in health and disease.
Funder: Wellcome Trust

Abstract: Dysregulation of the extracellular matrix (ECM) drives chronic diseases including osteoarthritis, fibrosis and cancer. Processes leading to dysregulation remain to be fully elucidated, though evidence shows that both the circadian clock and immune cells are involved in ECM deposition and turnover. My PhD will focus on collagen, the predominant component of the ECM. As an overproduction of collagen fibrils is the hallmark of conditions such as fibrosis, we will investigate how immune cells and the circadian clock influence collagen secretory pathways. Fibroblasts are the predominant ECM-producing cell type and their dysregulation is involved with driving progressive fibrosis. We will study the circadian clock in fibroblasts, with a particular focus on determining how clock-altering cross talk between immune cells and tissue-resident fibroblasts alters collagen synthesis and deposition. We will culture immune cells with fibroblasts expressing bioluminescently-tagged pro-collagen in order to quantitatively assess collagen fibril assembly. We will identify circadian clock-controlled proteins (CCCPs) using mass spectrometry tools. We will then use light microscopy to image matrix assembly in edited cells that are deficient in or constitutively expressing the identified CCCPs. This work will provide insight into collagen regulation and how the collagen secretory pathways can be subverted for therapeutic benefit.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: What is driving clonal expansion of mitochondrial DNA deletions?
Funder: Wellcome Trust

Abstract: Clonally expanded mitochondrial DNA (mtDNA) deletions are a major cause of mitochondrial disease and the underlying mechanism of oxidative phosphorylation (OXPHOS) deficient cells in ageing. Despite the importance of clonal expansion, we do not know how a single deleted mtDNA molecule accumulates within a cell. There are many previous hypotheses but none fully explain this process. Recently, I proposed and demonstrated that clonal expansion of mtDNA deletions originate from a perinuclear niche. However, why they accumulate in a perinuclear niche and how they spread to the rest of the cell is not yet understood. My proposal aims to: 1. Use subcellular analysis in human muscle samples to investigate the effects of mitochondrial morphology and mito-nuclear signalling on clonal expansion and assess the number of mtDNA deletion species present. 2. Use the Deletor mouse model to investigate the role of mtDNA replication and effect of modifying mitochondrial biogenesis on clonal expansion. 3. Use patient-derived induced pluripotent stem cells to generate a 3D skeletal muscle culture to assess the impact of modifying mito-nuclear signalling and interventions to prevent clonal expansion. This project will significantly advance understanding of an important pathological process and provide new avenues for therapy.

Lay abstract: Mitochondria fuel all the cells in the body and contain their own mitochondrial DNA (mtDNA). Over 1:5000 people have mtDNA mutations (e.g. large mtDNA deletions), which often cause devastating, untreatable diseases. There are hundreds of mtDNA per cell, so a single deleted mtDNA has little impact. However, mtDNA deletions accumulate throughout life leading to mitochondrial dysfunction. I have previously found that in skeletal muscle, this accumulation starts close to the nuclei, the cells’ control centre. In this project I aim to: Use human muscle to study the link between mtDNA deletions, mitochondria to nuclear communication and mitochondrial shape. Use a mouse model to understand how the replication of mtDNA and the production of new mitochondria impacts clonal expansion. Jointly grow human muscle and nerve cells in the lab, to use as a modifiable model. This work will help to understand how these diseases arise and progress, leading to future therapy.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: The Scar Free Foundation Programme of Research in Reconstructive & Regenerative Medicine
Funder: The Scar Free Foundation

Abstract: The aim of the primary research theme is to translate into clinical practice progress to date in developing 3D bioprinting technologies for engineering cartilage constructs for use in reconstructive surgery. The impact of this will be to improve outcomes in reconstruction and reduce or remove the need for using cartilage donor sites to ‘harvest’ tissue from elsewhere in the body, a process which is itself associated with scarring and a range of morbidities. In addition to clear patient benefits, improved surgical outcomes will bring important beneficial impact for clinicians and health-service providers. Looking to the longer term, the team aim aim is to broaden the application of our 3D bioprinting process to other tissue types to extend its utility to a wider range of conditions. The long-term goal is to be able to print a bioengineered composite ‘free flap’ with versatility to be used in a variety of surgical applications. Complementing the tissue-engineering work, our secondary research theme in big data aims to establish the prevalence of facial scarring in the population (initially in Wales, and subsequently for the rest of the UK); determine the incidence of associated psychosocial disorders; and identify risk factors for these.

Lay abstract: The primary focus of the new programme is the development and translation of the team's novel techniques for 3D printing soft tissue – initially cartilage – for use in facial reconstructive surgery. In addition, the team is developing existing collaborations and research in the area of ‘big data’ and health informatics to gain a comprehensive understanding of the prevalence, aetiology, impact (both psychological and physical), and outcomes of facial scarring in Wales.

Research activity codes: 5.3 MEDICAL DEVICES;5.4 SURGERY
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: Talk2Health Project
Funder: Innovate UK

Abstract: There are now half a million people in their 90s in the UK according to the Office for National Statistics (ONS), more than two and a half times the number in 1985\. By 2041 in the UK, the ONS estimates that there will be 3.2 million people aged 85 years and older. The incidence of MSK conditions increases as we age, through development of arthritis, loss of muscle tone and balance, and stiffening of soft tissues. Physical activity can impact all these physical changes and reduce pain leading to improved health, independence and socialising. In the UK, 40% of people 35-64 years of age live with an MSK condition, compared to 61% of those over 65\. Many elderly people report multiple MSK pain sites. Fractures, which are often a consequence of falls, are one of the most serious MSK problems seen in the older population. The Royal College of Physicians found that fractures and falls in people aged 65 and over account for over 4 million hospital bed days each year in England. As patients transition to digital, care models must be accessible and easy to adopt. Digital Health Consumer Survey 2020 reports over 60% of consumers would use digital health solutions if available. Healthcare providers must give equal access to healthcare for those in equal need, but widespread digital engagement relies on computer literacy hence online assessments can be challenging, particularly for those most disadvantaged in society. The goal of this project is to design and execute an easy-to-use humanised digital assessment and triaging/self-management solution to reduce pain, maintain mobility and encourage physical activity in an ageing and technology challenged demographic. The collaborators aim to improve PhysioWizard accessibility and engagement in the ageing population (55+ year-olds), by evaluating a range of voice-enabled options including pop-up avatar and simple voice enabled guidance, with a view to incorporating this technology to reach a far wider audience.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: Queen Mary University of London and Lucideon Limited
Funder: Innovate UK

Abstract: To transfer the knowledge of in vitro cell testing to ensure the optimisation and characterisation of materials used in medical devices and implants. To facilitate the innovation of novel formulations and concepts in biomaterials to improve the safety and efficacy of bone healthcare treatments.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);5.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE;MUSCULOSKELETAL
Title: Quantitative approaches to defining normal and aberrant protein homeostasis
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Cellular homeostasis depends on the presence of sophisticated quality control mechanisms that regulate the behaviour of proteins in their native and non-native states. A variety of diseases, which include systemic disorders such as type II diabetes and dialysis-related amyloidosis, and neurodegenerative conditions such as Alzheimer's and Parkinson's diseases, have been identified as being associated with incorrect processing of proteins in the cell. In this application we formulate a strategy for describing and potentially altering the behaviour of protein molecules in the cell, including their folding, misfolding and aggregation, based on a quantitative understanding of protein homeostasis. Our approach is based on the exploitation of the opportunities offered by technical developments in disciplines such as physics, nanoscience, chemistry and neurobiology. We have thus brought together researchers from such disciplines that have already an established track record of successful collaborations to put forward an ambitious programme to increase the level at which we can understand quantitatively cellular processes. The research at the Department of Chemistry will aim at the determination by a combination of experiment (Prof Dobson) and theory (Dr Vendruscolo) of multiple states of proteins, including partially folded conformations, misfolding intermediates, amyloid fibrils, and of the pathways of their interconversion. The activity at the Nanoscience Centre (Prof Welland) will involve the use of nanoscience techniques to establish quantitative relationships among different properties of proteins, including their aggregation rates and the mechanical properties of amyloids. At the Deparments of Genetics (Dr.Crowther) and of Medicine (Prof Lomas) we will use Drosophila models in conjunction with theoretical predictions to enhance our understanding of the origins of misfolding diseases and to explore the development of rational strategies for their treatment.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL
Title: To study the pain relieving effects of administering low-dose ketamine post-operatively to patients at high risk of developing chronic pain.
Funder: Department of Health (England)

Abstract: The study will commence with an audit of the prevalence of pain following thoracotomy and VATS procedures at 6 weeks. A double-blind randomised placebo control trial will be conducted to test the null hypothesis that an activated NMDA receptor does not determine the development of chronic post-surgical pain. Patients due to undergo thoracotomy will be recruited in out-patients and randomised to receive an intravenous ketamine infusion or placebo for 3 days post-operatively. Ketamine will be given in addition to the standard pain relief. Patients will be reassessed at 6 weeks, 3 months and 1 year to determine the long-term effects. Primary outcome measures will be the change in visual analogue pain scores. Secondary outcome measures will include: level of pain using the Brief Pain Inventory and the short form S-Lanss, modified quantitative sensory testing (QST), opioid and non-opioid analgesic consumption and the incidence of adverse effects.A second RCT will investigate the effect of an infusion of ketamine or placebo following VATS procedure, using a similar design and outcome measures. The underlying mechanisms of the action of ketamine will also be studied with regard to central sensitisation and wind-up.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL
Title: Evidence based prevention, identification and treatment of chronic fatigue syndrome (CFS/ME) in children and young people
Funder: Department of Health (England)

Abstract: Background: Chronic Fatique Syndrome (CFS/ME) is a common childhood condition with potentially serious consequences for those affected. The proposed research has 3 projects. Objectives: Project 1- Use population-based data to determine the prevalence of CFS/ME at age 13 and investigate risk factors for paediatric CFS/ME; Project 2- Investigate outcomes of care and compare three care models; Project 3-Develop a school-based early intervention to prevent development of CFS/ME and test its feasability and acceptability. Design: Project 1 Analyses of existing data from the ALSPAC birth cohort study Project 2 Expansion of existing longitudinal patient cohort to two additional paediatric clinical services using different models of service delivery; Project 3 Qualitative research followed by pilot intervention study Approaches: Project 1 Linear and logistic regression analysis, incorporating methods allowing for missing data; Project 2 Expansion of database, Linear and logistic regression models controlling for case mix; Project 3 Nurse-Led screening of young people with unexplained school absence, focus groups of parents professionals and children, development of tools to measure the economic impact of school absences Outcomes: Project 1 Novel and reliable estimates of prevalence of and risk factors for CFS/ME; Project 2 Improved understanding of outcomes of care based on the worlds largest paediatric cohort, credability to apply for further reading to create a national database; Project 3 An early intervention ready for testing using a full scale cluster RCT.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL
Title: System Identification and Information Processing for Complex Systems
Funder: Engineering and Physical Sciences Research Council

Abstract: The main aim of this Platform Grant proposal is to build upon the expertise of the Sheffield team in signal processing and system identification for nonlinear and complex systems to develop new research themes and application areas. The applicants developed the narmax methodology, a theory for nonlinear systems in the frequency domain, and a class of algorithms for the identification and analysis of spatio-temporal systems Recent developments at Sheffield mean we are now in a unique position to develop new multi-disciplinary research themes to exploit and build upon this expertise. The new multi-disciplinary research directions that we plan to develop as part of this research proposal include studies of drosophila brain, stem cell dynamics, diffuse optical tomography of brain, space weather systems, and crystal growth phenomena. Each of these offers unique challenges in signal processing and system identification and each requires scoping or feasibility studies to establish the potential to develop each new research area into a core research proposal. The core theme of this Platform Grant proposal is therefore to provide funding to conduct initial scoping research studies into each of these new multi-disciplinary projects with the objective that this will allow the development of each theme to the point where a responsive mode application can be submitted to take the research forward.Career development for members of our group including RA's is a core part of our strategy. The Platform Grant will provide stability for the collaboration by our research team with other disciplines, and should provide a critical mass of researchers and a longer term stable environment around which the career development of outstanding young researchers can be nurtured. The Platform Grant will enable the group to maintain the momentum that has been generated by the formation of two new research centres, and to build upon and exploit the multi-disciplinary partnerships that have been developed to date. The opportunity to take risks, try out completely new approaches, and completely new application fields produces an excitement in the research, enhances moral and longer term strategic research planning and development, allows flexibility, creates opportunities, and provides support for everyone in our group.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL
Title: CVD DIAMOND AS A SUBSTRATE FOR BIOLOGICAL CELL GROWTH - TOWARDS DIRECT BRAIN-COMPUTER INTERFACES
Funder: Engineering and Physical Sciences Research Council

Abstract: Controlling electronic devices using thought-processes may until recently have been in the domain of science-fiction. But brain-computer interface (BCI) research is showing that neural implants may allow computers, electronic equipment, or other mechanica


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;5.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE;NEUROLOGICAL