NIHRDataInsights/HRCSData huggingface dataset:
Title: Organelle dynamics
Funder: The Francis Crick Institute

Abstract: We are finding out how cells reshape their membranes and cytoskeleton when they divide. Our cells and many of the structures inside them (known as organelles) are encased in fatty membranes. When cells need to divide, they use molecular ‘machines’ to reorganise and distribute their organelles between daughter cells. One of these molecular machines is called the Endosomal Sorting Complex Required for Transport (ESCRT) and cells use this machinery to complete cell division and ensure that their new daughter cells contain functional organelles. ESCRT has many roles inside healthy cells, but it is also important when a cell is infected by certain types of viruses, as it helps to package viral particles in fatty membrane coats so they can be released. We are studying the ESCRT machinery in great detail to find out more about how it works and what can go wrong if it fails to do its job properly. We use high-powered microscopes, biochemical and molecular biological techniques to dissect how ESCRT functions. Our work focuses particularly on the role that ESCRT plays in reshaping the membranes around the cell’s nucleus – the structure where DNA is stored – as one cell divides in two. Understanding more about how the ESCRT machinery works tells us about some of the most fundamental processes of life at work within our cells, and helps to shed light on what might have gone wrong in a wide range of diseases.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Nudging Hospital Prescribers to choose the most Cost-Effective Medications
Funder: The Health Foundation

Abstract: Spend on medications is high and increasing. In 2015/16 the NHS spent almost £17 billion on medicines, an 8% increase on the previous year. As hospital prescribing accounted for nearly half this spend, it must not be ignored.(1) As prescribing is a behaviour, a behavioural intervention stands to affect it. We aim to examine if a behavioural intervention (i.e., presenting cost information) helps prescribers choose the most cost-effective medications. Evidence already suggests that such interventions can work without reducing care quality.(2,3)We will conduct three studies. In Study 1, we will modify the prescribing software already used at Heart of England NHS Foundation Trust such that prescribers see cost information at the moment they make a prescription decision. In Study 2, we will assess the intervention’s generalizability by asking prescribers at 18 other acute care trusts to complete simulated prescribing choices for the same medications. In Study 3, we will interview prescribing software experts to learn how they could implement our intervention swiftly, and write up our findings as a descriptive report and toolkit to be posted on Public Health England website, similar to the MINDSPACE report.(4) Study 3 is essential to ensure the spread of our intervention, as trusts use different software and encounter different obstacles to change.

Lay abstract: Spend on medications is high and increasing. In 2015/16 the NHS spent almost £17 billion on medicines, an 8% increase on the previous year. As hospital prescribing accounted for nearly half this spend, it must not be ignored.(1) As prescribing is a behaviour, a behavioural intervention stands to affect it. We aim to examine if a behavioural intervention (i.e., presenting cost information) helps prescribers choose the most cost-effective medications. Evidence already suggests that such interventions can work without reducing care quality.(2,3)We will conduct three studies. In Study 1, we will modify the prescribing software already used at Heart of England NHS Foundation Trust such that prescribers see cost information at the moment they make a prescription decision. In Study 2, we will assess the intervention’s generalizability by asking prescribers at 18 other acute care trusts to complete simulated prescribing choices for the same medications. In Study 3, we will interview prescribing software experts to learn how they could implement our intervention swiftly, and write up our findings as a descriptive report and toolkit to be posted on Public Health England website, similar to the MINDSPACE report.(4) Study 3 is essential to ensure the spread of our intervention, as trusts use different software and encounter different obstacles to change.

Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE
Title: Nudge based intervention supported by real time data analytics to improve ventilator weaning practice in critical care
Funder: The Health Foundation

Abstract: Critical care resources are limited, expensive and account for ~ 14% of a hospital's expenditure. Compliance to best practice is still sub-optimal with compliance being less than 50% to important live saving practices such as better ventilation. The reason for this failing is multi-factorial and interventions to alter the behaviour of critical care professionals are urgently needed.Critical care units have well established electronic health records and this lends itself to real time data analytics which could improve clinical practice through intuitive clinical decision support. In this project we will aim to improve ventilator weaning practice where multiple previous studies have demonstrated that up to 40% of a patient's ventilation could be spent weaning from ventilator. Weaning is also arbitrary, not directed or individualised.We will investigate two different nudge strategies to improve ventilator weaning, supported by the same clinical decision support tool which will issue alerts based on key ventilator & clinical variables. The two strategies are 1. Delivery of smart alert to bedside dashboard to nudge nursing behaviour & 2. Delivery of smart alert to doctor to nudge clinician behaviour.We will collect user acceptability, reduction in duration of CPAP mode of ventilation & other clinical outcomes in this proof of concept study.

Lay abstract: Critical care resources are limited, expensive and account for ~ 14% of a hospital's expenditure. Compliance to best practice is still sub-optimal with compliance being less than 50% to important live saving practices such as better ventilation. The reason for this failing is multi-factorial and interventions to alter the behaviour of critical care professionals are urgently needed.Critical care units have well established electronic health records and this lends itself to real time data analytics which could improve clinical practice through intuitive clinical decision support. In this project we will aim to improve ventilator weaning practice where multiple previous studies have demonstrated that up to 40% of a patient's ventilation could be spent weaning from ventilator. Weaning is also arbitrary, not directed or individualised.We will investigate two different nudge strategies to improve ventilator weaning, supported by the same clinical decision support tool which will issue alerts based on key ventilator & clinical variables. The two strategies are 1. Delivery of smart alert to bedside dashboard to nudge nursing behaviour & 2. Delivery of smart alert to doctor to nudge clinician behaviour.We will collect user acceptability, reduction in duration of CPAP mode of ventilation & other clinical outcomes in this proof of concept study.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;6.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Stand-alone walking stick
Funder: Versus Arthritis

Abstract: This is a project to address storing a walking stick safely and easily with minimal bending required by the user, allowing the stick to be easily retrieved when required.This product has a mechanism to allow a walking stick to stand up via two thin retractable spring steel legs, meaning that it can be stored on any flat floor. The user deploys the two legs when they require the stick to be free standing. When the user retrieves the stick, the legs are retracted inside the hollow body of the stick.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Innovative Water Pumps Enabling Better Healthcare
Funder: Wellcome Trust

Abstract: Thermofluidics has received a Translation Fund Award from the Wellcome Trust to develop an innovative, low cost irrigation pump to improve the health of malnourished smallholders in the developing world The solar powered water pump is based on entirely new technology with two components: the Non-Inertive Feedback Thermofluidic Engine (NIFTE) converts heat into fluid oscillations without moving parts and the Double Acting Hydraulic Ram (DAHR) uses fluid oscillations to generate shock waves that draw water from deep below ground and pressurise it at the surface. The NIFTE/DAHR is easy to maintain and can be manufactured from inexpensive materials (aluminium and plastics) using low cost production methods (moulding and extrusion). It has numerous other health-related applications including water pumping for drinking and sanitation, solar hot water provision, refrigeration, and oxygen enrichment of air. Tom Smith and Mark Bryant will lead the project, which will involve conducting developing-world field trials under controlled-conditions followed by stand-alone field trials of prototypes leased to farmers on working farms managed by Thermofluidics’ partners in India and Kenya. Thermofluidics aim is to conduct a pilot production-run and commercial launch at the end of the project. The project builds on a Wellcome Trust Interim project to develop a functioning pump suitable for a smallholder delivering superior performance to a treadle pump. The current project will design and fabricate a modular set of parts from which prototypes will be assembled to cover a wide range of low-lift and high-lift scenarios from open wells and boreholes. The intention is that Thermofluidics’ pump will ultimately improve crop yields, income and health outcomes for up to 550 million malnourished smallholders across the developing world.


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Flatworm Functional Genomics Initiative (FUGI) ME068077.
Funder: Wellcome Trust

Abstract: Despite the global impact of helminthiasis, lack of access to tractable experimental systems is severely hampering research progress. FUGI will advance this agenda by developing reverse genetics, genome-editing tools and immortal cell lines built around the thorough characterisation and understanding of parasitic flatworm stem cell systems. Application of CRISPR/Cas9 methods for facilitating flatworm genome-editing will grant unprecedented control over individual gene-level investigations. Use o f this technology to derive lines of knockout/knock-in flatworms will be assisted by our experience in harnessing retroviruses as germ-line, gene-transduction agents. Creation of immortalised flatworm cell lines, based on the proliferative potential of stem cell systems, will allow lifecycle-free, NC3R compliant, helminthology to proceed at pace. By applying tools of human stem cell science to parasitic flatworms, we will produce self-renewable resources for obtaining biological material, for o ptimising genome-editing tools and for generating homologous proteins suitable for functional investigations. FUGI will produce enabling resources (stored in community-accessible repositories) that will provide our field, for the first time, with the means to characterise the gene products responsible for parasite pathogenesis and persistence. These functional genomics tools will allow the helminth community to ask fundamental questions necessary to accelerate the development of novel anthelmint hic drugs and vaccines.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Complex Urban Systems for Sustainability and Health (London Hub)
Funder: Wellcome Trust

Abstract: The London Hub for Urban Health, Sustainability and Equity aims to be the world"s foremost transdisciplinary hub for research, training and pubic engagement on urban health. It is founded on two constituent projects - Complex Urban Systems for Sustainability and Health (CUSSH) and Pathways to Equitable Healthy Cities (PEHC) - and involves leading London-based institutions and their global network of collaborating institutions. The Hub"s principal objective is to integrate and coordinate research and stakeholder engagement that support evidence-based policies aimed at improving population health, health equity and environmental sustainability in cities around the world. The Hub, and its projects, will achieve this objective through comparative studies that involve participatory research and coproduction of knowledge among academic researchers, policy makers and practitioners, and civil society; developing models for prospective policy evaluation and applying these models to data from our partner cities; and training the next generation of research and policy leaders in urban health, while establishing the foundations for sustaining and expanding the Hub beyond the Wellcome funding period. The CUSSH project focuses on how to transform cities to address vital environmental and population health imperatives, and entails partnership with the cities of London, Beijing, Kisumu, Nairobi, Ningbo and Rennes.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Building a Blueprint for Action on Mental Health
Funder: Wellcome Trust

Abstract: There is a increasing recognition that mental health is a growing crisis ignored at the global level for too long. As a result, mental health is moving up the global agenda and there are a series of events in the next 6 months that will put mental health in front of decision-makers. This makes the next 6 months critical for setting the level of ambition and action by the international community and consolidating this attention into long-term, sustainable support. The global community, however, remains diffuse: groups focusing solely on their own aspect of mental health and not working strategically to leverage momentum. The GCFMH will address this short failing by gathering the community to create a blueprint for action for the mental health community along with unified messaging and narratives and advocacy asks. By providing the space, light-touch coordination and practical tools like policy briefings, narrative support and messaging, GCFMH aims to bolster the community to become greater than the sum of it parts and build a drumbeat for action on mental health over the next six months and into 2019. This proposal request £247,346.00 in funding over a 6 month period from 15th August 2018 to 31st January 2019.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Biomolecular mechanisms underlying cellular responses to nonthermal electromagnetic fields: getting to the ‘heart’ of the matter
Funder: Welsh Government Office for Science

Abstract: The main goal of my proposal is to understand the fundamental non-thermal biological effects of alternating electromagnetic fields (EMFs). In order to tackle this long-standing issue, I will establish an expert team of independent, interdisciplinary researchers, spanning three schools within Cardiff University. This Fellowship will build on my strong background in multidisciplinary research developed during my current position as a National Research Network Sêr Cymru Research Associate (NRN062). During the Fellowship I will develop and test a novel experimental system which will revolutionise research into the biomolecular mechanisms of action of EMFs. To do this I will utilize a coplanar waveguide platform in order to deliver EMFs of varying frequency (50 Hz and 2.45 GHz) and power intensity to biological samples. For the first time, this will enable microscopic observation of EMF-induced molecular changes in real-time using fluorescent/ phosphorescent probes targeted to key intracellular processes. Special focus will be placed on investigating the role of EMFs in enhancing or disrupting cell-cell communication: a matter of life or death in many biological systems. In order to determine whether the elucidated mechanism of action of EMFs is evolutionary conserved across two domains of life, experiments will be conducted on the bacterium Vibrio fischeri as well as human embryonic stem cell-derived cardiomyocytes (hESC-CM). Outcomes of this research will impact healthcare, facilitating optimized design and delivery of EMF-based therapeutic devices, and will influence the review of current industry standards for the safe limits of exposure to EMFs.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Signalling and Transcription
Funder: The Francis Crick Institute

Abstract: Cellular signal transduction pathways cause specific activation of gene transcription, but much remains to be learned about the mechanisms involved, and the links between transcription and cell behaviour. We focus on the transcriptional regulator SRF and its cofactors, the MRTFs and TCFs, which controls proliferation and cell adhesion/migration in response to external factor and mechanical stimuli. The MRTFs are novel G-actin binding proteins belonging to the RPEL family, and are targets for a novel signal pathway, the Rho-actin pathway, which allows their activity to be coordinated with actin dynamics. We also study the molecular biology of other RPEL proteins, including the Phactr family of PP1 cofactors, and the ArhGAP12/32 families of rho GAPs. We use approaches ranging from biochemistry, structural biology and cell biology to studies of cancer and immune mouse models in knockout mice. We pursue several inter-related research topics:  The biological roles of the MRTF/SRF pathway, focussing on (i) its role in proliferation, transformation and senecence, and (ii) its role in the response to mechanical stress, and (iii) its role in cell adhesion and motility, using cancer, immune and cell culture models.  G-actin controls MRTF nuclear import and export, phosphorylation, transcriptional activation, and SRF interaction. We use structural, cell biological and biochemical approaches to study these regulatory events.  Biology and regulation of the Phactr family of PP1 cofactors, with a focus on Phactr1. We seek to identify Phactr/PP1 substrates in different settings, and understand the basis for substrate recognition by the Phactr/PP1 holoenzyme. Complementing this is the study of the role of Phactrs in cytoskeletal regulation, aiming to understand the functional significance of their regulation by G-actin.  Functional analysis of the ArhGAP12 family of rhoGAPs, focussing on ArhGAP12. We seek to understand what it is about the function of these GAPs that requires their coupling to actin dynamics. Our emphasis is on cytoskeletal regulation in cancer cell invasion and metastasis.  Development of approaches to measure signal strength in the Rho-actin signalling pathway which controls the activity of RPEL proteins. These will be applied in the various cell and in vivo models employed above.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Versatile mRNA display strategies to manipulate protein citrullination
Funder: The Francis Crick Institute

Abstract: The functional human proteome is vastly expanded by post translational modifications (PTMs). PTMs are intimately involved in gene regulation and have profound effects (either individually, or in combination) on protein structure and function, finely tuning the reactions of a cell. One such PTM, protein citrullination is catalysed by five structurally-related isozymes, the peptidyl arginine deiminases (PADs). Dysregulation of citrullination and PAD activity has been linked to numerous diseases including rheumatoid arthritis, multiple sclerosis and various cancers and likely plays key roles in early development and fertility. Emerging evidence implies that PAD inhibition has significant therapeutic potential. PAD enzymes have a wide range of substrates within a cell, but the functions of individual citrullination events remains poorly characterised. Current inhibitors of PAD4 primarily bind to its active site, inhibiting all catalytic activity, making it challenging to dissect the function of individual citrullination events. Compounds that disrupt individual protein-protein interactions (PPIs), such as those that target PAD4 to specific genomic loci or substrate proteins, without blocking catalytic activity would enable selective modulation of subsets of PAD4 citrullination activity. From a basic science perspective, such tools would help to dissect the individual roles of, for example, subsets of PAD4 target genes in a manner that is difficult to achieve through genetic manipulation and in the longer term might provide powerful pharmaceutical agents with reduced side effects. My lab aims to develop selective tools to modulate PAD4 activity by identification of peptides from an in vitro transcription/translation cyclic peptide discovery platform known as the RaPID system. To do this, new strategies for enrichment of cyclic peptides from the RaPID system to allow tailored selection for functions other than generic binding are being developed. We are producing targeted inhibitors and activators of specific PAD isozymes, including peptides that inhibit only subsets of a given PAD isozyme’s enzymatic activity. To study localisation, activity and binding interactions in cells, peptides will be further functionalised, for example with fluorescent dyes or photoreactive groups. Through a multi-disciplinary approach combining chemical, structural and cell biology, we hope to use these tools to connect the biochemical effects of protein citrullination with biological function; a field in which there has been relatively little work compared to many other PTMs. Additionally it will be possible to extend our new selection strategies to other protein targets.


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