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Results

LifeLines 20 Apr 2016

This is the expansion of a project supporting volunteers aged 50 plus to run activities for vulnerable older people to improve health and well-being. These have previously included art classes, creative writing, yoga and computer club. The group will expand across the city, recruiting more volunteers, supporting more than 800 new people and establishing a Men’s Network to encourage older men to socialise regularly. It will also extend its HealthLink scheme to help older people get to medical appointments.

Kilkeel RBL - Saving Our Community Venue 22 Oct 2015

The group is a community and voluntary based organisation providing a range of services and activities to the local community. They received a grant of £10,000 to make improvements to their venue so that it can be used for more classes and activities.

Grant to Royal British Legion Tipton Branch 19 May 2016

Remembering Tipton's World War One Heroes

Grant awarded to The Royal British Legion (Forest Hall) Branch And Club (Tyne & Wear) 20 Nov 1998

Towards improving access and facilities for disabled people at the Forest Hall Ex-Servicemen's Institute.

Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 13 Jul 2004

To provide daycare services to older people living in high rise flats in Newcastle.

Biomedical Vacation Scholarship 25 Jun 2012

Not available

Amount: £7,020
Funder: The Wellcome Trust
Recipient: University of Liverpool

Profiling and characterising differential deubiquitylase activity during the cell cycle 12 Jul 2011

A family of around eighty deubiquitylases (DUBs) can reverse the effects of ubiquitylation to stabilise proteins, or regulate their activity and localisation. Whilst phosphorylation, dephosphorylation and ubiquitylation play well-established roles in cell cycle progression, our understanding of the role for deubiquitylation is less developed. In a preliminary screen using immunoblotting for tagged ubiquitin activity probes we identified changes in the activity of specific DUBs between mitotic and interphase cell extracts, including USP7 which was highly active during interphase, but inactivated at mitosis. The key goals of this studentship are to: 1. Systematically profile changes in enzymatic activity for the family of DUBsduring key transitions of the cell cycle using pull-down of tagged ubiquitin activity probes coupled with mass spectrometry. 2. Elucidate the mechanism by which cell cycle-dependent DUB activity is regulated. For USP7, and other key cell cycle-regulated DUBs we identify, we will investigate cyclical changes in their phosphorylation status, cellular localisation, and protein interactions. 3. Provide mechanistic insight into the role of these DUBs during the cell cycle. We will establish whether appropriate USP7 regulation is crucial to the deubiquitylation of key substrates, or to normal cell cycle progression using expression of non-regulated mutants.

Amount: £146,279
Funder: The Wellcome Trust
Recipient: University of Liverpool

Lactate and myometrial function: an investigation into the effects and mechanisms of action. 14 Dec 2010

1. To determine the effects of extracellular lactate on force and calcium signalling in uterine smooth muscle 2. To examine lactate production and pH during normoxia and hypoxia 3. To determine the expression of lactate transporters (Mono-Carboxylate Transporter, MCT1-4) in the myometrium and how this changes with gestation in rats 4. In women having Caesarean Section (CS), to correlate measurement of lactate in myometrial capillary blood with indication for CS and in vitro contractility and lactate production.

Amount: £14,897
Funder: The Wellcome Trust
Recipient: University of Liverpool

Investigation of the role of Nrf2 in man 15 Mar 2011

This research proposal aims to address the question of whether the Nrf2 transcription factor pathway is a critical regulator of cellular defence in man. In order to answer this question, sensitive and specific biomarkers are required that will allow us to define the natural variability of the system in the human population, and also the extent to which Nrf2 activity can be induced by exposure to drugs and other chemicals. Nrf2 is a transcription factor that, in animal models, regulates the adap tive cellular response to chemical stress, including up-regulation of antioxidant proteins, drug metabolizing enzymes and cellular transporters, each aimed at reducing the potential chemical hazard. Our recent proteomic investigation of Nrf2 null mice also points to an important role in hepatic lipid metabolism. Using a combined proteomic and metabolomic approach, we will characterize tissue and biofluid samples from three different experimental models: Nrf2 null mice, hepatocyte-derived rodent and human cell lines and freshly-isolated human hepatocytes. These studies will yield candidate biomarkers which will undergo performance analysis in two proof of concept studies, using samples obtained from a panel of patients treated for 7 days with the Nrf2 inducer, resveratrol, and in a longitudinal cohort of paracetamol overdose patients.

Amount: £301,447
Funder: The Wellcome Trust
Recipient: University of Liverpool

Consent Methods in Paediatric Emergency Medicine and Urgent Care Trials . 20 Sep 2011

This project will engage with key normative questions to investigate how consent is and ought to be conducted in paediatric emergency care (EC) trials, providing empirical evidence, informed by bioethical literature to produce normative guidelines to optimise trial recruitment. The empirical component will use a mixed method design involving children and young people (aged 7-16 years), families, practitioners and members of the research community. Goals will be to: map the nature of consent methods in UK EC paediatric trials; explore experiences and attitudes to different consent methods; and explore the concept of informed consent in EC trials. The ethical review component will explore key normative questions, and reflect upon the value of social and public health perspectives on bioethics, particularly conceptions of solidarity (research for the common good), within an area that has so far been dominated by individual rights-based approaches. The reflective equilibrium method (RE ) will be used to integrate empirical evidence and ethical literature, generating new knowledge in the field of biomedical ethics and leading to the formulation of guidance for the design and conduct of consent in paediatric EC trials for the research community. Outputs will be disseminated through academic, public and clinical healthcare routes.

Amount: £168,881
Funder: The Wellcome Trust
Recipient: University of Liverpool

Value in people award. 21 Oct 2008

Not available

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Liverpool

Open Access Awards. 16 Sep 2008

Not available

Amount: £30,000
Funder: The Wellcome Trust
Recipient: University of Liverpool

Role of Palmitoylation in Neuronal Function in C. elegans 29 Aug 2008

The overall aim of this project is to determine the role of protein palmitoylation in neuronal function in vivo, using Caenorhabditis elegans as a model organism. Specific objectives are: 1. To characterise the behavioural phenotypes resulting from the systematic mutation of all predicted protein palmitoyl acyl transferases and thioesterases. 2. To determine the tissue-specificity and subcellular localisation of these enzymes. 3. To identify neuronal palmitoylated substrate proteins and their palmitoylation sites 4. To investigate the role of site-specific palmitoylation in the function of selected neuronal proteins.

Amount: £139,388
Funder: The Wellcome Trust
Recipient: University of Liverpool

An investigation of the effects of H2S on myometrial function. 29 Aug 2008

Recent findings on the biological role of Hydrogen sulphide (H2S) have led to the suggestion that its role may be as significant as that of nitric oxide. In the studies to date made on smooth muscles a relaxant effect has generally been reported. In the field of uterine smooth muscle finding new tocolytic (relaxant) mechanisms and therapeutic targets is a major goal, as premature labour is the principle cause of neonatal mortality and a major cause of handicap. Very little however is known about how H2S can influence myometrial activity. The aims of this project are therefore to: 1) Measure Ca transients and contractility produced spontaneously, by high-K depolarization and via oxytocin stimulation in the presence of increasing amounts of H2S 2) Determine if responses to H2S are altered during pregnancy and labour 3) Examine in myometrium which enzymes are responsible for the production of H2S 4) Informed by the data obtained in the above aim, an investigation will be made into the mechanism by which H2S affects uterine activity by measuring membrane currents and/or myosin light chain phosphorylation, intracellular pH and sarcoplasmic reticular function.

Amount: £139,388
Funder: The Wellcome Trust
Recipient: University of Liverpool

Wellcome Trust Clinical PhD Programme at the University of Liverpool. 15 Jul 2008

Oxidative stress is implicated in the pathology of many lung diseases including chronic obstructive pulmonary disease, pulmonary vascular disorders and asthma. The epidemiological association of respiratory and cardiovascular disease, and high levels of particulate matter in the atmosphere may be explained by dysregulation of redox balance. This project will examine the implications of oxidative stress on human alveolar macrophage (AM) behaviour. Specifically, we wish to explain the extent to which extrinsic oxidative burden may cause intracellular redox imbalance, and the degree to which, in conditions of chronic exposure, enzymatic antioxidant defence protects against detrimental cellular effects. Although studies of lung epithelial lining fluid provide some evidence of extracellular disturbance, the intracellular component in humans is not well studied. Studies will include in vitro and ex vivo observations of macrophage susceptibility to oxidative toxicity from bacterial products, including pneumolysin (a key virulence factor produced by common respiratory pathogen Streptococcus pneumoniae). We will assess to what degree this susceptibility is augmented by redox imbalance secondary to selenium deficiency and smoke exposure (from cigarettes and indoor wood fire) We hypothesise that, in macrophages already under oxidative stress, there will be higher rates of apoptosis, and decreased antibacterial function in terms of oxidative burst and phagocytic capacity. If proved, this would have direct implications for the prevention of pneumonia.

Amount: £61,257
Funder: The Wellcome Trust
Recipient: University of Liverpool

Value in People Awards. 29 Mar 2010

Not available

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Liverpool

Open access award. 22 Sep 2009

Not available

Amount: £45,000
Funder: The Wellcome Trust
Recipient: University of Liverpool

Wellcome Trust Clinical PhD Programme at the University of Liverpool. 08 Jun 2009

The incidence of stroke has increased in low income countries; Malawi is an example of this. A 40% increase in four years in the hospital population has been described. One third of these individuals with stroke are young without established vascular risk factors but are HIV seropositive. HIV infection may be contributing to this increased incidence of stroke. I will examine the relationship of HIV infection and stroke in Malawi and test the primary hypothesis that individuals with HIV infection have an increased risk of stroke compared with community controls. The results could facilitate the rational use of therapies for HIV and vascular disease in primary and secondary prevention, and direct research in novel targeted therapy. The Key goals are: 1. To determine the risk factors for stroke in Malawi, integral to this will be to describe the impact of HIV alone and in combination with other vascular risk factors on the nature and aetiology of stroke 2. To determine the role vascular risk factors and/or HIV infection has in predicating a poor prognosis 3. To gain an insight into the pathogenesis by describing the relationship between endothelial function and stroke in HIV infected individuals

Amount: £69,916
Funder: The Wellcome Trust
Recipient: University of Liverpool

Structural modulation of amyloid fibrils and intermediates by glycosaminoglycans. 28 Apr 2009

We propose to explore how the molecular mechanism of assembly of disease-linked amyloid species are influenced by glycosaminoglycans (GAGs). We will focus on two important examples of disease-linked amyloid, namely, amylin, associated with type-2 diabetes mellitus, and Abeta1-40, associated with Alzheimer's disease. Solid-state NMR will be used to compare the structure of oligomeric and fibrillar aggregates formed from isotopically labelled peptides assembled with/without heparan sulphate (HS) a nd various GAG analogues. The key goals are: 1. To determine how the presence of GAGs during fibril growth affects the structure of amyloid protofilaments of Abeta and amylin. 2. To identify and describe in atomistic detail the nature of the molecular recognition event between amyloid fibrils of amylin and Abeta with different structural architectures and the GAGs heparin and heparin sulphate (HS). This will be achieved by measuring couplings between isotope labels strategically placed in the peptide precursors and using novel heparan sulphate derivatives prepared by chemically modification to incorporate isotope labels. 3. To examine the effect of GAGs on the mechanism of assembly of amylin and Abeta into amyloid fibrils by the characterisation of transient oligomeric intermediates trapped using rapid freeze-quench followed by their structural analysis using solid state NMR.

Amount: £183,563
Funder: The Wellcome Trust
Recipient: University of Liverpool