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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.

Newcastle Animal MRI Centre 03 Mar 2011

The animal MRI facility in Newcastle allows the characterisation of the anatomy and system-level organisation of brain mechanisms for perception, attention and higher cognition. The work develops a model of normal and abnormal brain organisation that can be realistically compared with that in man and used to inform detailed animal studies at the neuronal level. The facility in Newcastle allows key collaborations with groups in the USA and Europe interested in system-level organisation relevant to human cognition, on the one hand, and neuronal-level mechanisms, on the other. We require a critical upgrade to the scanner to allow parallel imaging providing increased resolution and improved signal-to-noise ratio for structural imaging (anatomy), diffusion imaging (tractography) and BOLD data (functional studies). The equipment and additional member of support staff requested will allow work with the following biological objectives: 1) high resolution anatomical definition of area s that are investigated using invasive techniques (recording) and non-invasive techniques (fMRI); 2) investigation of the connections of cortical and subcortical regions and 3) increased speed and resolution for BOLD imaging. The award would allow the continued viability and further development of work toward an efficient animal model for the normal and diseased human brain.

Amount: £372,900
Funder: The Wellcome Trust
Recipient: Newcastle University

Systems Neuroscience: From Networks to Behaviour. 31 Aug 2011

Our overarching aim is to understand·the·. spatial and temporal patterns of activity during neocortical seizures. Ultimately, we want to understand what happens at the edge of seizure, at the boundary between core recruited territories, and surrounding areas where firing is suppressed by an inhibitory restraint (penumbral territory). This boundary may or may not be fixed; in some instances, the penumbral territory is subsequently recruited, in which case the boundary shifts, but in other instances, further recruitment is prevented, and the boundary remains fixed. A key goal therefore is to understand these two possible outcomes, namely the recruitment of new territories or the failure to spread. · Prior work has indicated that the boundary may be set by an inhibitory restraint of the penurhbral territory. We will study epileptic activity patterns in several relevant transgenic mouse lines, and also in vivo and in vitro human recordings. Various studies have shown that raised intraneuronal Cl levels are found in epileptic tissue. Low intraneuronal Cl is required for functional GABAergic inhibition, and so raised intraneuronal Cl may lead to a disinhibited network. We will investigate the role of Cl dysregulation in the failure of the restraint.

Amount: £149,515
Funder: The Wellcome Trust
Recipient: Newcastle University

Regulation and function of p52 and Bcl-3 NF-kB subunit complexes. 09 Mar 2011

Activation of the 'alternative' (non-canonical) NF-kB pathway leads to processing of the p100 precursor subunit to p52. Activated p52 containing complexes, together with the p52 coactivator Bcl-3, regulate the adaptive immune response and recent studies have demonstrated the importance of this pathway in many diseases, including cancer. However, the functional differences between different p52 containing complexes are poorly understood, while the role of different post-translational modificatio ns has not been defined. We propose that the p52 homodimer/Bcl-3 complex has particular importance as a pro-proliferative, pro-metastatic and tumour promoting transcription factor, particularly in breast cancer. Importantly, recent evidence suggests that formation of this complex is regulated by p52 phosphorylation. By complementing the expertise of the applicants' laboratories, we plan to transform our understanding of the function of p52 and Bcl-3 NF-kB complexes by linking state of the art mechanistic analysis to physiological significance and disease progression. Specifically we will (1) Investigate the regulation and function of the p52/Bcl-3 complex (2) Develop novel knock-in mouse models to allow us to investigate p52 function in vivo (3) Define the role of p52 and Bcl-3 in breast cancer and determine their ability to act as disease modifiers

Amount: £1,008,588
Funder: The Wellcome Trust
Recipient: Newcastle University

The telomere cap in budding yeast. 14 Oct 2010

To define the roles of different proteins at telomeres of budding yeast we aim to understand: 1. Roles of specific gene products at uncapped telomeres. We will carefully analyse the effects of specific gene products on growth, cell cycle progression, checkpoint kinase activation, ssDNA accumulation and other processes in yeast cells containing uncapped telomeres. Through such experiments we will infer the in vivo biochemical function of the corresponding gene products. 2. Telomere repli cation. We will use a number of complementary methods to understand the interaction between the DNA replication fork and the telomere cap. We will address whether the newly synthesized 5' lagging strand, the previously synthesized 5' strand, or both are degraded after telomere cap failure. 3. Genes affecting the telomere cap and telomere replication. We will apply Quantitative Fitness Profiling (QFP) to tens of thousands of robotically generated double mutant yeast strains with telomere or D NA replication defects. We will extend QFP to telomerase deficient cells and to quantify the effect of over-expression libraries on the growth of cells with a telomere capping mutation. We will develop QFP algorithms and computational architecture, utilizing more advanced statistical and visualization techniques, to extract more value from the experimental screens.

Amount: £492,025
Funder: The Wellcome Trust
Recipient: Newcastle University

Two-component signalling in Candida albicans. 10 Nov 2008

Stress responses are intimately linked with the pathogenicity of Candida albicans, the major systemic fungal pathogen of humans. We have found that diverse environmental stress responses are dependent upon the stress-activated protein kinase (SAPK) Hog1 in C. albicans. However, little is known about how environmental signals are sensed and relayed to the Hog1 pathway. We and others demonstrated in model yeasts that two-component signalling pathways act to relay stress signals to SAPK pathways. S ignificantly, our pilot experiments in C. albicans have shown that the two-component response regulator protein Ssk1 is required for the response to a specific subset of environmental signals that also requires the Hog1 SAPK, indicating Ssk1 to be a major regulator of Hog1. We have also identified a novel two-component signalling protein Crr1 in C. albicans, and our analysis illustrates that Crr1 is important for the oxidative stress response in a mechanism independent of Hog1 activation. This t imely proposal which builds on this strong platform of data has two key goals: (i) to define the two-component signal transduction network that relays environmental signals to the Hog1 SAPK, (ii) to characterise the mechanism of action of the novel two-component protein Crr1 in mediating the oxidative stress response.

Amount: £190,148
Funder: The Wellcome Trust
Recipient: Newcastle University

Development of statistical methodology for detection and characterisation of genetic factors in complex disease. 06 Apr 2009

The aim of this project is to develop statistical genetic methodology for the detection and characterisation of genetic variants predisposing to complex traits (including both quantitative traits and disease phenotypes). Work will be focussed in the following four areas: 1. Model selection and data-mining methods for modelling the effects of multiple loci, and selecting those loci that are most likely to be causative 2. Imputation and haplotype-based approaches for detection and modelli ng the effects of untyped genetic variants 3. Modelling the effects of maternal genotype, maternal-foetal interactions and imprinting in genetic association studies 4. Correcting for correlations between related individuals in family-based association studies, in the presence of missing genotype data The key goals of the project will be to publish details of the methodology we develop in reputable, peer-reviewed scientific journals and, where appropriate, to produce and distribute co mputer software implementing the methods. These dual goals will allow other researchers to make use of the methods that we develop in their own genetic studies. A secondary goal will be to apply the methods developed to real data sets from studies of human complex being conducted by my collaborators.

Amount: £795,074
Funder: The Wellcome Trust
Recipient: Newcastle University

Ontogeny and function of human dermal dendritic cells. 17 Jun 2009

Dendritic cells (DC) are critical agents in the induction of immune responses and potential targets of immunotherapeutic interventions. To date, human studies have largely relied on in monocyte-derived DC generated in vitro. Much less is known about migratory myeloid DC in the peripheral tissues such as the skin, lung and gut where they acquire antigen and are mobilised to the draining lymph nodes. Recent research has defined the migratory myeloid DC of the human dermis and reveals two subsets differentiated by CD1a and CD14 expression. In this proposal my goals are: 1. To investigate the relationships between primary dermal DC, inflammatory DC and monocyte-derived DC 2. To map the human DC subsets to homologous DC subsets in the mouse 3. To determine whether CD1a+ DC may be derived independently of monocytes in the steady-state 4. To determine the key functional differences between CD1a+ and CD14+ DC 5. To test whether dermal DC are in vivo loaded with melanocyte antigen s and if this can induce tolerogenic or lytic immune responses Realisation of these goals will provide new insights into the induction of immune responses and improve our understanding of ways to enhance immunotherapeutic approaches.

Amount: £653,878
Funder: The Wellcome Trust
Recipient: Newcastle University

Determinants of Participation and Quality of life of adolescents with cerebralpalsy: a longitudinal study (SPARCLE 2) 14 Oct 2008

During adolescence, rapid physical and psychological changes occur which may be more difficult for disabled adolescents. We will examine to what extent pain, impairment,psychological health, parental stress and environmental factors, all amenable to intervention, influence participation and quality of life (QoL) of disabled adolescents. We will follow up the 818 children aged 8-12 yearswith cerebral palsy studied in2003-4 in an EU funded Project, co-ordinated by the principal applicant; the children were sampledfrom nine European regions with population-based registers. We will re-visit these children when adolescents, seeking to identify preceding and contemporaneous determinants of their participation and QoL. As in the earlier study, the conceptual framework will be the International Classification of Functioning, Disability and Health which bridges the social and medical models of disability. We seek 30 months funding to visit the 316 adolescents from the three UK and Irish red and two are seeking funding for the visits. The results will provide evidence for policy development in health, education and social sectors; and for trials of intervention.

Amount: £264,470
Funder: The Wellcome Trust
Recipient: Newcastle University

Systems neuroscience: From networks to behaviour - Impact of maternal deprivation on cortical gamma oscillations. 19 May 2010

Early life stress (i.e., a period of social deprivation or neglect occurring in postnatal life) is associated with a variety of neuropsychiatric outcomes in adult life. These include depression, post-traumatic-stress disorder, panic disorder, schizophrenia, attention deficit disorder and an abnormal stress response. Stress exposure in early life is also associated with deficits in cognitive function, including impaired spatial learning and memory. Little information exists concerning the impact of early life stress on cortical rhythms of cognitive relevance. Using a rodent model of early life stress, the ability of cortical circuits to generate neuronal oscillations implicated in cognitive function, will be examined. Specific aims to be addressed in cortical slices from control and maternally deprived rats are: 1) What is the impact of maternal deprivation for gamma oscillation generating circuits in a number of critical cortical regions? 2) Can differences between gamma oscillations in control and MD cortical circuits be explained by a reduction in the expression of specific interneuron subclasses? 3) Assess the longitudinal impact across lifespan of MD for cortical gamma oscillations.

Amount: £146,795
Funder: The Wellcome Trust
Recipient: Newcastle University

Systems neuroscience: From networks to behaviour - Role of identified interneurons in motor processing. 19 May 2010

1. By combining the use of several different pharmacological and neurophysiological measures formulated in vitro, we aim to identify cortical inhibitory interneurones (IIN) in vivo based on their extracellular spiking 2. These methods for interneuron identification will be used to: a. Assess how interneuron activity modulates during preparation and initiation of voluntary movement b. Determine how intracortical and peripheral stimuli activate different interneuron classes c. Determine how interneurons contribute to the generation of spontaneous beta-band oscillations within the primary motor cortex

Amount: £146,795
Funder: The Wellcome Trust
Recipient: Newcastle University

Solid-state electrode arrays for multiple intracellular recording. 29 Mar 2010

1) To construct a solid-state alternative to conventional glass micropipettes for intracellular recording of transmembrane potentials in neurons during network activity. 2) To implant multiple solid-state electrodes in an array suitable for multi-channel parallel intracellular recordings.

Amount: £9,942
Funder: The Wellcome Trust
Recipient: Newcastle University

Neuroimaging and neurophysiology of syntactic learning 01 Jul 2010

This project aims to address the questions: What aspects of the syntax of auditory or visual sequences can animal models learn? Which brain regions support animal model syntactic learning and how is the putative network interconnected? How do neurons evaluate the structure of the sequences, and how do the fMRI and neuronal responses relate? We will address these questions, as follows: First, animal models will be exposed to training sequences exemplifying an arbitrary grammatical rule, foll owed by evaluating their natural-response preferential-looking behaviour to grammatical and ungrammatical sequences. Second, animal models will be used to reveal the brain regions sensitive to grammatical violations, including how the fMRI-identified regions are interconnected (based on white-matter tractography and combined microstimulation and fMRI, which we have used recently to reveal effective connectivity in vivo). Third, we will record from neurons in two of the fMRI-identified brain reg ions to reveal how neurons from these regions support syntactic learning.

Amount: £453,181
Funder: The Wellcome Trust
Recipient: Newcastle University

Cardiac manifestations of mitochondrial disease - incidence, mechanisms and treatment. 03 Dec 2009

Mitochondrial DNA (mtDNA) diseases affect more than 1 in 10,000 people and exhibit variable clinical features. Cardiac manifestations are common and include conduction abnormalities and cardiomyopathies. In patients with mitochondrial disease, I wish to: 1. determine the incidence and nature of cardiac manifestations; 2. understand the molecular mechanisms linking different defects to different cardiomyopathies; 3. demonstrate the effect of early intervention on energy metabolism. To determine the incidence of cardiac manifestations, I will have access to the MRC Mitochondrial Disease Patient Cohort (UK). Clinical assessment will be performed using ECG, echocardiography and Holter monitoring. To understand the molecular mechanisms underlying specific cardiac defects, I will use a bank of fresh-frozen cardiac tissue from patients with different mtDNA mutations. I will use different histochemical, immunohistochemical and molecular genetic techniques to explore the nature of the molecular defect in individual cardiomyocytes from patients with specific genetic defects. Magnetic resonance imaging and 31P spectroscopy will be used to determine the incidence of early cardiomyopathic changes and bioenergetic defects due to different mtDNA mutations. I will repeat studies following 3 months of treatment with energy-sparing agents to establish whether these changes are reversible and whether early medical intervention in high risk groups is justified.

Amount: £244,514
Funder: The Wellcome Trust
Recipient: Newcastle University