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Results

Improving the engagement of pregnant/early postnatal women in research 16 Jan 2018

It is challenging to engage pregnant/early postnatal women with local maternity research, as pregnancy is a normal physiological process which is relatively short-term, and after which women find regular engagement challenging. As such, two different engagement approaches will be piloted by University-based researchers and Patient and Public Involvement advisers to engage local pregnant/early postnatal women in research development, recruitment and dissemination on a continuing and regular basis. Both approaches will involve local researchers coming to speak to women about the latest maternity research and opportunities for involvement. One approach will attach this activity to an existing class at a children’s centre, whilst the other will be attached to a new yoga and midwifery advice session developed as part of this project. Information provided during these sessions may be useful to women during their pregnancy or after they have had their babies, and the insights of women will help to ensure the research is relevant and has the best chance of success. Women will help researchers translate research findings into a format suitable for a range of audiences. The groups will be evaluated and, if successful, plans will be made to make the group self-sustaining.

Amount: £16,000
Funder: The Wellcome Trust
Recipient: University of Birmingham

The ethical governance of Artificial Intelligence health research in Higher Education Institutions 26 Jul 2018

Artificial Intelligence (AI) is increasingly being used in health research in areas such as genomics, medical imaging/screening, and health prediction of epidemics and disease outbreaks [1-6]. AI research has the potential to improve health outcomes but raises urgent, complex moral questions, including issues of AI design bias; AI's black-box nature and inherent lack of transparency; and the ownership of algorithms used in AI and the data they produce [6-12]. Such ethical issues challenge Higher Education Institution (HEI) ethical governance systems, which traditionally focus on notions of risk, consent and privacy in human participant research [13]. To preliminarily explore how we can move towards making these governance systems more appropriate for HEI AI health research, this project employs empirical methods to map one aspect of the AI research area, and explore the views, experiences and understandings of relevant scholars on: the usefulness of current HEI governance systems to oversee the types of ethical decisions they make during AI research; collaborating with the private sector and associated ethical concerns; their responsibility towards post-research/implementation issues associated with AI; and the need for specific ‘health research’ ethics governance. The goal is to make/disseminate preliminary recommendations to improve HEI ethical governance for AI health research.

Amount: £84,751
Funder: The Wellcome Trust
Recipient: King's College London

Public data, private collaborator: Will machine learning relocate medical knowledge? 26 Jul 2018

This study focuses on the transformations in the creation and ownership of medical knowledge that result from applications of machine learning (ML). In medical image recognition, ML applications are currently being developed and tested to assist in diagnostics. These developments are often carried out as collaborations between public and private sectors, with public medical institutions providing data and medical domain knowledge, and private technology companies providing ML expertise. However, the algorithms implemented in these tools are typically proprietary, trade secrets that underlie the competitive advantage of the companies that develop and operate them. There consequently limited transparency into and access to the medical knowledge that they generate. This knowledge is thus privatised in the sense that it is encapsulated within closed software that forms part of the IPR of a private company. This study analyses such risks of privatisation and the role of open data in medical research. By comparing cases of ML applications in Ophthalmology, by conducting semi-structured interviews with stakeholders and organising two participatory workshops, the project will examine the role of data ownership and explore measures that allow medical knowledge to be kept in the public realm while still attracting private collaborations for ML applications.

Amount: £57,307
Funder: The Wellcome Trust
Recipient: King's College London

Regulating healthcare through blockchain: Mapping the legal, ethical, technical and governance challenges 30 Nov 2017

Blockchain technologies have the potential to radically reshape many industries, including healthcare. These technologies create a distributed database across a network of computers, using cryptographic methods to verify the consistency of digital records and transactions. This could enable the secure, tamper-proof, transparent, and trustworthy management of health-related data. But some doubt whether blockchain can deliver on its promise. Others fear that it will deliver too much, providing efficiency and security without sufficient operational sensitivity to healthcare contexts. Blockchain is a form of ‘design-based’ regulation, entailing the hard-coding of regulatory norms into systems infrastructure and operation. For example, by creating a transparent and unalterable audit trail regarding data access and usage, or by building in privacy through data encryption. Hard-wiring norms (e.g. traceability and privacy) into healthcare systems might overcome shortcomings of conventional legal and ethical regulation, but is likely to face major implementation challenges. This project will identify, map, and examine the implications for utilising blockchain in healthcare. It will identify the legal ethical, technical, and governance opportunities, risks, and challenges. It will thereby begin to explore whether, and under what conditions, these technologies might be developed whilst remaining faithful to important ethical, democratic, and constitutional values.

Amount: £94,757
Funder: The Wellcome Trust
Recipient: University of Birmingham

Biomedical Research and the Politics of the Human 30 Jul 2018

The human is a primary reference point for the aims of contemporary biomedical research along with its ethical and political groundings. This project asks: what and who constitutes that human? Despite the many assumptions we may hold about what and who is human, no study has delivered fine-grained empirical research about how scientists, policymakers and regulators approach and define the human across the levels of cells, tissues, and organisms. A series of changes—in biomedicine and in the scholarship on science and society—signal that it is a crucial time to reconsider the meaning and function of the human in the life sciences. Using an inductive qualitative approach, this project offers an ambitious plan for an empirical reorientation with the human in relation to two domains of biomedicine that constitute the project’s work packages: 1) Kidney Organoids: miniature organs grown in petri dishes. 2) Interspecies Mammalian Chimera: injecting human cells into developing pig embryos Based on a theoretical framework that draws together insights from science and technology studies, sociology and legal and political studies, the project is built on detailed empirical observation of the two research domains covering four national case studies in the UK, Spain, Germany and USA.

Amount: £629,823
Funder: The Wellcome Trust
Recipient: King's College London

Decolonising madness? Transcultural psychiatry, international order and the birth of a global psyche 07 Mar 2018

Are mental illnesses and the core concepts in the psychiatric toolkit universal and identical across cultures, ethnic groups and 'civilisations'? This research will offer the first substantial historical analysis of the roots of the current global mental health movement and transcultural psychiatry. It challenges the idea that the concept of a global psyche is a recent development, and aims to demonstrate that it emerged in the aftermath of WWII and during decolonisation, when Western psychiatry endeavored to leave behind its colonial legacies, and lay the foundation for a new union of Western and non-Western concepts of mental illness and healing. In this period, leading psychiatrists across the globe set about identifying and debating the universal psychological characteristics and psychopathological mechanisms shared among all cultures. My research will explore this psychiatric, social and cultural search for a new definition of 'common humanity', and analyse the core medical-historical forces behind it. The International Pilot Study of Schizophrenia will serve as a case study. The project will involve the scoping of archives in Europe, Africa, Asia and the US, the employment of four research assistants, organisation of an international conference, and the creation of a network of researchers and practitioners in global psychiatry.

Amount: £28,155
Funder: The Wellcome Trust
Recipient: University of Exeter

MA Literature and Culture PT 30 Jun 2018

My research will use literary material to contextualise the reception of medical texts and diagrams in late medieval Europe. The research refers to medical diagrams found in western manuscripts produced between the 13thC and 15thC named homo signorum (zodiac man). The project argues that this image and the widely-known Galenic humoral theory influenced travel writers in their descriptions of non-European bodies. This medical information was not understood neutrally, and was received as referring to Western, European, male bodies. The research develops the work of Susan Conklin Akbari (2009) and Irina Metzler (1997), contributing towards the emerging recognition within Medieval Studies of prejudiced interpretations and applications of medical theory within medieval literary texts. A medical discourse was developing in the later Middle Ages which conceptualised race as biological. A 13thC scientific discourse claimed that non-European peoples partook in a ‘blood libel’, which involved restoring a natural flux of the melancholic humor through drinking the blood of male Christian children. Medieval understandings of physiology were conflated with literary representations of the deviant non-European body. This research aims to investigate the unbalanced, unhealthy bodies presented within travel narratives, which deviate from the Western-European normative ideal of health interpreted from medical texts and diagrams.

Amount: £24,000
Funder: The Wellcome Trust
Recipient: University of Birmingham

Waiting Times 01 Feb 2017

This project brings together an interdisciplinary team to investigate waiting as a cultural and psychosocial concept, and an embodied and historical experience, in order to understand the temporalities of healthcare. It represents a fundamental rethinking of the relation between time and care through a critical analysis of waiting in the modern period. Working across Medical Humanities and Psychosocial Studies, we will uncover the history, cultural representation, and psychosocial organisation of delayed and impeded time, from 1860 to the present. This work will underpin focused investigations of ‘watchful waiting’ in current general practice, psychotherapy, and end of life care. We ask which models of time operate within healthcare practices and develop new models of durational temporality to conceptualise how waiting can operate as a form of careful attention, historically and in the present. Contextualising these healthcare practices within broader social organisations of time, we open up the meanings, potentialities, and difficulties of waiting in current times. Through academic publications and extensive public engagement, we will reframe debates about waiting in and for healthcare, moving beyond the urgent need to reduce waiting times in the NHS, towards a more comprehensive understanding of the relation between waiting, care, and changing experiences of time.

Amount: £674,829
Funder: The Wellcome Trust
Recipient: University of Exeter

Senior Fellowship (WHO Placement & Global Health Justice Research) 30 Sep 2017

This proposal seeks support for an 18-month senior fellowship. The fellowship enables (1) placement at WHO GHE unit to help develop an ethical framework for ageing policies (‘just global ageing policies’) through a global, collaborative and comprehensive multi-stakeholder and multi-sectoral process, and incorporating WHO policy related documents. The framework would be informed by the fellow's (Venkatapuram) expertise in health justice philosophy and the capabilities approach previously cited by the WHO in the 2015 World Report on Ageing and Health. An ethical framework for addressing the needs of a specific social group (elderly) would be a distinctly new type of output for bioethics and the WHO compared to ethical guidelines for specific disease interventions or events (epidemics). The fellowship also enables (2) philosophical research on global health justice. Venkatapuram seeks to extend his argument for a human right to the capability to be healthy (CH)--presented in Health Justice (Polity, 2011) and in the WT funded project Population Level Bioethics and CA (WT 094245))--to global health governance and institutions. The research outputs will include two journal articles, short commentaries, lectures, and a monograph. The monograph proposal is being developed with Harvard University Press. 40% of time will be spent on this research.

Amount: £151,279
Funder: The Wellcome Trust
Recipient: King's College London

3i outreach - disseminating data, methods, analyses and knowledge 05 Dec 2016

An essential goal of the 3i Strategic Award is the provision of "high-end" data in open-access format. The approved plan was to send all data to the Wellcome Trust Sanger Institute (WTSI) and the European Bioinformatics Institute (EBI) who run the website of the International Mouse Phenotyping Consortium (IMPC). However, WTSI discontinued public data display in favour of contributing to the IMPC site (www.mousephenotype.org). Therefore, WTSI’s change in policy jeopardises our capacity to achieve an essential goal. Addressing this, we have allocated IT resources to establish a 3i website (www.immunophenotype.org), enabling users to search and appropriately analyse 3i data. This proposal will address the outlined issues by making sure both websites are updated with fast turnaround times, use the same statistics, score the same hits, use the same graphs, display flow data at different levels of complexity, and each offer optimal query options for their respective target groups, immunologists (3i) and a wider scientific community (IMPC), respectively.

Amount: £200,808
Funder: The Wellcome Trust
Recipient: King's College London

Imaging visuomotor transformations in the brain 30 Nov 2016

A central goal of sensory neuroscience is to understand how the brain builds internal representations of the external world and how these representations guide decision making and behaviour. For example, what patterns of activity in the brain allow an animal to distinguish prey from predator and how does this activity trigger the appropriate behavioural response? To address this fundamental problem we will use the optic tectum of larval zebrafish which converts visual information from the retina into hunting and escape behaviours. Thus, the tectum must generate distinct visual representations, prey vs predator, which biases a decision between mutually exclusive responses - move toward or away. To understand how the tectum does this we will combine high speed functional imaging of every neuron in the tectum with video recording of eye and tail movements. These approaches will allow us to describe how visual information is encoded in the tectum and to define the activity patterns that drive eye and tail movements associated with either approach or avoidance behaviours. Our project will generate new insights into how the brain enocdes visual information and the nature of sensory representations that drive behaviour.

Amount: £1,600,547
Funder: The Wellcome Trust
Recipient: King's College London
Amount: £63,702
Funder: The Wellcome Trust
Recipient: University of Exeter

The genetic control of collective cell migration: insights from the neural crest 12 May 2017

Collective cell migration refers to the movement of a cell population that acquires directionality through cell-cell interactions. All cells of the group may be capable of reading directional cues, or they may divide their labour with front cells, ‘leaders’, indicating the path to rest of the group. The precise molecular signals that control cell identities and behaviour in the context of collective cell migration remain unclear. We have studied this process in Neural Crest (NC) cells, a highly migratory population that arise early during embryogenesis. Our recent work has demonstrated that zebrafish trunk NC (TNC) migrate collectively and present non-exchangeable leader and follower identities. The firm allocation of TNC identities strongly suggests these are transcriptionally regulated. In this project, we will generate new NC zebrafish reporter lines that will allow the specific labelling of TNC populations by photo-conversion (leader, follower or premigratory). Labelled cells will be then isolated and processed for RNA-Seq. These data sets will allow us to characterize leader, follower and premigratory cells transcriptomic signatures. This is an essential step towards the elucidation of the genetic networks controlling TNC identities and behaviour.

Amount: £99,939
Funder: The Wellcome Trust
Recipient: King's College London

How does nonsense-mediated decay contribute to gene regulation in developing neurons? 31 May 2018

Nonsense mediated decay (NMD) is a quality control mechanism used by eukaryotic cells to destroy messenger RNAs containing incorrectly positioned translation termination codons [1]. NMD, in combination with alternative RNA splicing (AS), also provides a potent mechanism for natural changes in gene expression in developing brain [2-5]. The main goal of my summer project will be to test the hypothesis that progressive down-regulation of an RNA-binding protein called PTBP1 during mammalian neurogenesis promotes neuronal identity by changing AS patterns and triggering NMD of multiple neural precursor-specific transcripts. I will first follow up on the RNA sequencing screen carried out in the Makeyev lab and validate bioinformatically predicted AS-NMD targets using Reverse Transcription PCR and quantitative PCR analyses of developing nervous system samples and embryonic stem cells undergoing neuronal differentiation in vitro. I will then analyse AS-MND regulation for one example showing the most robust regulation. This will be achieved by designing minigene and CRISPR-Cas constructs specific for AS-NMD promoting exons and testing these reagents in mouse ES cells undergoing neuronal differentiation or treated with siRNA against PTBP1. The results of this work should improve our understanding of the AS-NMD pathway and evaluate its contribution to neuronal differentiation.

Amount: £0
Funder: The Wellcome Trust
Recipient: King's College London

Elucidating allosteric processes in immunoglobulin E 31 May 2018

Immunoglobulin E (IgE) is thought to be the first line of defence against parasitic pathogens, mediating immune reactions by binding to either of its two receptors, either the high-affinity FcepsilonRI receptor or the low-affinity CD23 receptors. While the IgE molecule was previously thought to exist in a primarily acutely bent conformation in solution, Drinkwater et al. (2014) found that IgE was able to exist in a fully extended conformation while Davies et al (2017) showed that omalizumab (XolairTM by Novartis) trapped IgE in a partially bent state to block its action on its FcepsilonRI receptors. The McDonnell Laboratory has derived a series of anti-IgE antibody Fab fragments, selected for their ability to affect IgE’s overall structure and dynamics and consequently to allosterically affect the binding to IgE’s receptors. In this proposed study, we will investigate how observed ligand-mediated changes in conformational dynamics manifest themselves as entropically-driven allosteric modulation. As a complement to NMR studies of ligand-mediated changes in protein dynamics, currently ongoing in the McDonnell Laboratory, direct measurements of the thermodynamic parameters of ligand binding will be performed using isothermal titration calorimetry.

Amount: £0
Funder: The Wellcome Trust
Recipient: King's College London

Determining The Intrathymic Mechanisms That Instruct Regulatory T-cell Production For Control Of Organ Specific Autoimmunity 30 Sep 2018

T-cells recognise and mount an immune response against pathogens however responses against self-tissue can occur, causing tissue damage and disease. In the thymus (a unique organ of T-cell development and education) autoreactive T-cells are removed but this isn’t 100% efficient, meaning a sub-population of T-cells termed regulatory T-cells (Tregs) is required to prevent self-reactivity. Our understanding of Treg development is incomplete and has been further challenged by findings of high heterogeneity in the thymic Treg population i.e. a large population of mature vs de novo Tregs. Furthermore possible Treg development outside the thymus by the most recent thymic emigrants (RTEs) remains unexplored. To accurately assess Treg development we use a novel mouse model with fluorescent markers that identify both a) Treg vs. non-Treg, and b) age. Distinguishing a cells identity along with its age allows us to investigate new and old Tregs in the thymus as well as Treg RTEs in the periphery using techniques such as flow cytometry, microscopy and qPCR to characterise thymic and extrathymic developmental stages. This work will provide new insight into how Tregs which regulate discreet tissue sites are generated, offering valuable new information on an essential regulator of self-reactivity and disease.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Birmingham

The role of inflammation in the formation of multi-drug resistant lineages of Escherichia coli 30 Sep 2018

Multi-drug resistant (MDR) Escherichia coli and Klebsiella pneumoniae are the new superbugs of the 21st century. Strains of these bacteria are now commonly being isolated which are resistant to all front line clinical antibiotics, as well as last line compounds such as colistin. In the absence of new effective antibiotics we must find new ways of combatting such infections. Data generated by our lab suggests that the main genetic difference between MDR E. coli and normal harmless E. coli is the presence of signatures of natural evolutionary selection in genes involved in anaerobic metabolism, which are utilised by E. coli in an inflamed environment. We will test the hypothesis that the ability to better live in inflamed intestinal environments led to the formation of MDR strains of E. coli, which can outcompete other bacteria and set up long term infections. We will further test if this can be countered using simple anti-inflammatory measures.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Birmingham

Transformations: Encountering Gender and Science 16 Jun 2018

The Rethinking Sexology team’s historical research has uncovered important material on the relationship between medical authority and ‘patient’ experience and the development of diagnostic categories/treatment protocols. We propose a public engagement programme that invites young trans people (age 16-25) to explore this material, co-conduct new research, including an oral history project, and develop an ambitious programme of creative responses leading to a performance and exhibition in four relevant high-profile venues across the UK. The plan of action has been developed during an extensive consultation period with key stakeholders, in which ideas and methodologies have been fully tested. The programme is led by the Rethinking Sexology (RS) team who has an outstanding track record in field-leading engaged research and public engagement. The team’s experience will be complimented by collaborating with a uniquely qualified group of writers, performers and youth-facilitators, known for their pioneering and award-winning work with the trans community, with whom the RS team already has long-standing collaborative relationships. The programme will deliver a set of exceptionally innovative activities that will empower young people to: contribute to and enhance health and humanities research and public engagement practices; investigate clinical and diagnostic protocols and transform clinical dialogue; shape public debate through high-quality creative outputs (exhibition/performance) that promise to be intellectually, artistically and emotionally powerful and stimulating. The co-production model at the heart of the programme will feed systematically and continually into ongoing research activities, enabling the project to stand as a beacon of good practice in engaged research and public engagement.

Amount: £147,315
Funder: The Wellcome Trust
Recipient: University of Exeter