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Results

A taste of hard work: assessing the utility of ancient tartar to track exposure to respiratory irritants of occupational origin in ancient skeletal remains 23 Jan 2018

My proposed cross-disciplinary research will elucidate the potential of ancient tartar to reveal exposure to a variety of respiratory irritants and their links to health in past societies by unlocking the signature of inhaled/ingested occupational debris and pollutants generated during crafting. Applying state-of-the-art microscopic methods in Archaeology and Physics, and working both with experimental archaeology and ancient skeletal material, my project aims to: analyze the full range of micro-particles (dietary and environmental) entrapped within the tartar of Roman and Medieval individuals to assess exposure to respiratory irritants, with a strong focus on those of occuational origin; characterize exposure to and inhalation of microscopic particles and pollutants produced during selected craft activities (e.g., pottery, textile production, woodwork) using experimental archaeology (i.e. microscopic occupational ‘signatures’); critically assess how micro-debris in calculus can be linked to other archaeological parameters to elucidate the involvement of ancient individuals in crafty activities and their link to health; expand our understanding of air pollutant exposures associated with traditional craft production, often carried out within developing societies as a means of poverty alleviation.

Amount: £245,659
Funder: The Wellcome Trust
Recipient: University of York

EVIPNet Europe policy and research scoping tool 18 Jun 2018

I propose to develop a policy and research prioritisation tool for use by EVIPNet Europe countries to improve knowledge translation between research and policy. The goal would be to create a ranking system to help health policy decision-makers pinpoint high-priority policy issues that would benefit from research input in clarifying the problem or framing options for its solution. It should also aid research policy decision-makers to identify where to invest research resources, taking into account policy needs, to create implementable recommendations. Such a tool would encourage decision-makers to analyse quantitative data, for example the burden of disease, and qualitative information, such as public attitudes, and reach agreement when allocating resources to programmes. To create it I would complete a scoping literature review on the merits of various existing tools and combinations of tools. I would gather a variety of evidence, including systematic reviews of best practice, and case studies from the region that explain how these tools have been adapted to work in similar settings. I would consult with the EVIPNet country knowledge translation networks on their particular research and policy needs and challenges so as to select and adapt a context appropriate design for the tool.

Amount: £14,388
Funder: The Wellcome Trust
Recipient: University of York

Memory and silence: The role of miRNA machinery in tolerisation of macrophages 31 Jan 2017

Macrophages are key mediators of immune responses. Upon encountering microbial antigens, macrophages become activated, which results in pathogen phagocytosis and clearance, and initiation of the adaptive immune response through antigen presentation and inflammatory cytokine secretion. However, uncontrolled macrophage activation can lead to acute systemic inflammation and organ damage (septic shock). Interestingly, exposure to low levels of antigen results in macrophages becoming hypo-responsive following subsequent stimulation (macrophage tolerisation). Furthermore, myeloid cells within a tissue display remarkable heterogeneity in cytokine production. However, the role of population heterogeneity on macrophage tolerisation remains unknown. MicroRNAs are small regulatory RNAs that repress gene expression. They can also decrease noise (stochastic fluctuations) in protein expression and regulate cell-to-cell variability of gene expression. We propose that microRNA-mediated regulation of population heterogeneity is a key mechanism involved in macrophage tolerisation. Here, we will characterize population heterogeneity in wild type and microRNA-deficient (globally or single microRNA) macrophages. We will generate stochastic models to predict phenotypic (tolerisation) switches and validate mathematical outcomes empirically. This research will demonstrate how microRNAs regulate innate immune responses and provide new routes to improve infection and vaccination outcomes.

Amount: £16,771
Funder: The Wellcome Trust
Recipient: University of York

Investigating seizure manifestation in Rett syndrome 31 May 2018

Seizures in epilepsy and other neurological disorders have a devastating effect on patients and their families. Due to their amenability for genetic manipulation, mouse models of neurological disorders where seizures represent a significant comorbidity represent an exciting opportunity to pinpoint these alterations. One such disorder is the devastating neurological disorder, Rett syndrome (RTT) that affects 1 in 10,000 females. Seizures represent one of the most debilitating symptoms observed in RTT, are frequently atypical absence seizures, lead to a worsening of other symptoms and are often refractory to treatment. Despite their high prevalence, the underlying cellular and circuit mechanisms leading to the manifestation of RTT-associated seizures remain unknown. During this award, I characterise the mechanism of spike-and-wave-type discharges (SpW), a marker of atypical absence seizures, in a mouse model of Rett syndrome. Furthermore, I will evaluate whether reducing the activity of a particular subset of interneurons is sufficient to prevent the generation of SpW activity in these mice. Together, the results from this proposal will uncover the causally important cell types responsible for seizure manifestation in RTT and identify potential new strategies for the control or prevention of these seizures.

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

Extracting patterns across memories to guide decisions 15 Aug 2016

How do we use past experience to guide behaviour and how does this process break down in specific patient populations? I will develop a novel experimental-computational tool to understand how individuals transform memories of previous events into generalised models of the world that allow them to behave appropriately in the future. For past experience to guide behaviour, we need to extract generalities or patterns across a set of events. Pattern extraction allows us to predict what will happen in novel but related situations. I will develop a new experimental technique in healthy humans (based on rodent research), where participants are required to extract patterns across a set of past events in order to make accurate predictions about future events. I will build computational models to predict and explain behaviour at the level of individual people. The models will assess what pattern a participant has extracted, and how this differs from the pattern that would optimise future predictions. Critically, when an individual is not behaving appropriately, the experimental-computational technique will reveal what is impaired and why. In the future, this technique will be used as a microscope to pinpoint impairments in memory-guided decision-making in patient populations.

Amount: £92,955
Funder: The Wellcome Trust
Recipient: University of York

Assessing the effect of ZO3 overexpression on tight barrier formation proliferation and differentiation in normal human urothelial cells. 01 Apr 2016

Tight junctions are cellular structures that are implicated in epithelial barrier function. Preliminary data indicates that the zonula occludens protein, ZO3, is important in tight junction formation during differentiation of urinary tract urothelial cells. This project will examine the effects on tight junction formation, cell proliferation and differentiation in normal human urothelial cells engineered to overexpress ZO3 through the use of retroviral transduction. My hypothesis is that ZO3 overexpressing cells will show an enhanced barrier function as assessed by TER levels. Further, these cells will show an increased differentiation capacity and reduced proliferation compared to control, non-treated cells. To test this, cell culture and tissue engineering techniques will be used to grow and differentiate the cells, as well as TER to assess barrier function and immunocytochemistry to localise the expression of ZO3 in overexpressing and control cells. In addition, RTqPCR will be used to quantify amount of ZO3 transcript expression and western blotting will be undertaken to confirm protein overexpression. The results of this experiment should offer some novel insights on epithelial biology and might inform the development of new therapies for bladder diseases.

Amount: £1,500
Funder: The Wellcome Trust
Recipient: University of York

Investigating Flagellar Motility of Leishmania spp.; its Impact on Parasite Lifecycle Progression and Infectivity 30 Sep 2016

Leishmaniasis is a chronic, debilitating disease that is the second biggest killer amongst parasitic diseases. It is caused by the obligate, intracellular protozoan Leishmania spp. [1] which undergoes a complex life cycle transitioning between promastigote and amastigote stages in sandfly and human hosts, respectively[1]. The different lifecycle forms each have a different aim. Whether that aim is migration within the sandfly’s midgut or infection of leukocytes, each involves motility of the promastigote form to enable the lifecycle to progress. We will use a myriad of techniques to examine the role of parasite motility in Leishmania : host interactions – investigating movement parameters, fluid dynamics and evidence of chemotaxis to compare different promastigote lifecycle forms. We hypothesise that studying the biophysical swimming parameters and biomolecular factors may reveal good therapeutic targets to block Leishmania spp. transmission to human hosts and/or invasion of mammalian immune cells. With the aim of correlating motility at individual, population and genetic levels this could elucidate the Leishmania parasite’s mechanisms for survival and transmission to human hosts.

Amount: £7,324
Funder: The Wellcome Trust
Recipient: University of York

Biomedical Vacation Scholarship 22 Jun 2015

Not available

Amount: £8,000
Funder: The Wellcome Trust
Recipient: University of York

Establishment of the Northern Network of Medical Humanities Research . 31 Mar 2014

This bid proposes seven day-length research workshops for members of the Northern Network of Medical Humanities. Through these workshops, we aim to facilitate collaborative research within the NNMH by strengthening understandings of the research interests and expertise within the network. It will create a forum for interdisciplinary discussions of work in progress and allow members to build connections with non-HEI partners (charities, arts organisations, clinicians) in each of the workshop venu es. The proposed workshops will run from June 2014 - June 2016 and will be held at various NNMH member institutions. The first introductory workshop will be funded separately by Durhams CMH. Funding is sought for the remaining six workshops. The bid will also support the development of a website to showcase and disseminate the work of the Northern Network. The workshops will complement a series of training events for doctoral students in the medical humanities scheduled to start in 2014 and s upported by a recent AHRC Collaborative Skills Award. In addition, the bid proposes three meetings of the Networks Steering Committee to plan and make decisions about the appropriate contents of the workshops and to guide responses to possible collaborative grant calls.

Amount: £7,950
Funder: The Wellcome Trust
Recipient: University of York

The Nature of Religion, Science and Health. 31 Mar 2014

A major academic event that will discuss the links between religion, science and health, from medieval times to the present day. Built around keynote addresses presented by four leading historians of science, medicine and health, the event will also involve a panel of influential respondents drawn from academia and religion to debate the points made in the keynote addresses. The event, which will be organised at the Theatre Royal in York and/or the York Minster, will then involve a detailed roun d-table discussion, and general question and answer session. These discussions will be chaired by major public figures (the University is currently in discussion with Melvyn Bragg, Jeremy Paxman and Rowan Williams to join the programme). This two day event will also be made a part of the York Festival of Ideas so that a very serious public engagement activity gets included and to ensure that the audience is large.

Amount: £4,980
Funder: The Wellcome Trust
Recipient: University of York

Making sense of the ethics of gestational time in the abortion clinic: A comparative analysis of clinical and lay understandings. 17 Mar 2011

Drawing on insights generated by the recent turn towards the sociological analysis of ethics in practice (e.g. Haimes, 2002; Hedgecoe, 2004; Wainwright et al., 2006; Williams, 2006; Ehrich et al., 2007; Cribb et al., 2008), the proposed research addresses a novel set of questions about the ethics of abortion. Empirically, the research will explore the ways in which patients and health professionals understand the ethical significance of gestational time in abortion decision-making, the ethical dilemmas that they face concerning temporality, and the implications of the ways in which its meaning is negotiated by both participants in the health professional-patient relationship. Conceptually, it will compare conventional clinical framings of personhood and temporality in the context of abortion with the alternative theorisations of this issue which are offered by feminist bioethics/philosophical work. Normatively, it will use insights from the conceptual and empirical analyses to explor e routes towards the improvement of patients and health professionals experiences.

Amount: £150,165
Funder: The Wellcome Trust
Recipient: University of York

Hyperpolarisation using SABRE as a new tool for imaging. 17 Apr 2012

Diseases of the nervous system, of infectious and non-infectious origin, have global impact on human health and are often associated with neuroinflammation. Approximately 0.5M people in the UK suffer from Alzheimers disease and research shows such classical neurological diseases, may be associated with systemic-inflammation. One core challenge in understanding brain disorders is it remains extremely difficult to non-invasively probe the underlying neurochemistry, the blood-brain barrier and the neuroinflammatory response. During the Award, we will: i) develop and validate new methodologies for spin-hyperpolarised MRI that can theoretically improve a 1.5T clinical-MRI systems response by 200,000-fold; ii) implement the technology for applications spanning molecular and cellular, tissue and organ, system and whole-organisms; iii) achieve first-in-man studies with it; iv) use it to study perfusion, blood-brain-barrier, microglial activation and models of neurological disease; v) trai n a new generation of interdisciplinary post-doctoral researchers; vi) produce an internationally recognized hub facilitating worldwide uptake of these methods. In this programme we target the development of specific high sensitivity spin-hyperpolarised compounds that produce signals that encode their spatial distribution and simultaneously their role in biochemical and physiological mechanisms. These probes will test hypotheses regarding the blood-brain-barrier, microglial activation, neuro nal function and metabolism in models of neuroinflammatory conditions.

Amount: £3,607,868
Funder: The Wellcome Trust
Recipient: University of York

Master's Studentship 12 Jul 2011

Not available

Amount: £18,705
Funder: The Wellcome Trust
Recipient: University of York

"New directions in the histories of health, healing, and medicine in African contexts" to be held in South Africa 25 Jun 2012

A two-and-a-half day workshop comprising paper presentations, overviews, round-table discussions and mentoring of senior graduate students, with the following three main goals: - To bring together and establish a network of scholars working on histories of health, healing and medicine in Africa, and more especially Southern Africa. - To build research capacity of scholars, including upcoming researchers from disadvantaged backgrounds and institutions, based in Southern Africa. - To share work-in-progress and/or proposals for future workshops, research projects and publications - including with research partners at the Wellcome Trust. The timing of the workshop is sparked by a visit to South Africa by Professor David Wright (McGill University) who is the keynote speaker and his work on both mental disability and on African health-care workers in transnational medicine promise to be important for scholars across several disciplines. Other themes to be explored include: methods, methodologies, archives and ethics; healing and trauma; epidemics and epistemes; the profession of biomedicine and African doctors; healthcare workers and indigenous beliefs about illness; hospitals and local economies; healthcare, welfare and development; gender, faith, service and identity in mission hospitals; and the politics of post-apartheid health insurance and macro-policy.

Amount: £6,550
Funder: The Wellcome Trust
Recipient: University of York

The neural basis of familiar face perception. 04 Feb 2009

1: What facial information is used to represent identity? Findings from cognitive psychology show that face recognition is a holistic process. We will identify whether holistic processing of identity is characteristic of all face regions, or restricted to those thought to be involved in recognition. We will then demonstrate whether shape or texture cues dominate this representation. 2: Are different neural codes used to represent familiar and unfamiliar faces? The ability to recognise fam iliar faces across a variety of image changes has been integrated into cognitive models of face processing. We will ask whether an image-dependent or image-invariant neural code is used to represent familiar faces. We will then determine whether the neural code that is used to represent the configuration of familiar faces is different to that used for unfamiliar faces. 3: How are dynamic and static cues used for recognition? Because faces can be readily recognized from photographs, most stu dies of face recognition ignore the role played by dynamic cues. However, recent studies have found that movement can play an important role in face recognition. A key question, we will address is whether the same or different brain regions are involved in recognition with static and dynamic cues.

Amount: £193,857
Funder: The Wellcome Trust
Recipient: University of York

A combined in vitro and in virtuo multi-scale approach to understanding calcium signalling as a signature and integrator of cellular response. 04 Feb 2010

An integrated process of computational model development, quantitative experimentation and iterative cycles of simulation and hypothesis testing will be used to characterise calcium signals generated during epithelial scratch-wounding and explore how these are translated into individual cell response and emergent tissue behaviour. Calcium-signalling and cell response will be monitored in scratch wounded uro-epithelial cell cultures. Candidate receptor and ion channel expression will be inferred from pre-existing transcriptome data and confirmed functionally using agonists/inhibitors. These data will be used to inform modules of a computational model incorporating different mechanisms of calcium release and signal transmission. The calcium signature (amplitude and duration) experienced in response to a specific stimulus will be mapped to the resultant cell response and used to inform a software agent model that will be used to explore wound healing as an emergent context-specific prop erty of individual cell response. The key goals are 1) Characterisation of calcium signalling mechanisms during urothelial self-repair. 2) Integrate calcium signalling with individual cell response in a nondeterministic agent-based computational model in order to investigate emergent field properties. 3) Develop an extensible computational tool for biologists to relate calcium signalling and cell behaviour in different tissues and situations, such as compromised wound healing.

Amount: £371,918
Funder: The Wellcome Trust
Recipient: University of York

The Medical Category 'Bites and Punctures' in Latin Medical Literature in the 13th-14th centuries. 26 Nov 2009

The medical category of bites and punctures (de morsu) in late medieval medical literature in Western Europe included those of both venomous and non-venomous animals. My goals are: to understand how the category was defined and situated in the learned medical tradition and the elaboration, use and disuse of this medical category by Western medical writers. to use this as a case in the study of textual medical categorisation; to investigate how it was structured in regard to causes, sym ptoms, and treatment, whether similar or unique in each author, with the aim of placing into context medieval theoretical and practical ideas on puncture wounds caused by animals and animal toxicology to carry out a controlled companion enquiry into the category s presence in preaching materials, to test hypotheses about preaching as a means of mass dissemination of medical ideas.

Amount: £139,762
Funder: The Wellcome Trust
Recipient: University of York

Vacation Scholarships 2008. 27 May 2008

Not available

Amount: £5,760
Funder: The Wellcome Trust
Recipient: University of York

Open Access award. 31 Oct 2006

Not available

Amount: £10,000
Funder: The Wellcome Trust
Recipient: University of York