- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 18 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
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 Menâ€™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 Â£10,000 to make improvements to their venue so that it can be used for more classes and activities.
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.
We will exploit the opportunities of the UK National Health Service to generate a national resource of human iPS cells and associated data. We will generate and bank lines from 700 healthy and 800 disease-associated individuals, optimising techniques for iPS cell production and quality control. Cells will be subjected to extensive analysis of genome, epigenome, gene expression and proteome. For cells from healthy individuals, in-depth analysis of inter-individual variability will provide an open access platform for association studies of cellular function, and for distinguishing pathological from physiological variation. Patient collections will be selected via an open call, focusing initially on well-characterised conditions, where a single genetic lesion underlies a pleiotropic clinical phenotype. To characterise cellular phenotype we will construct high throughput artificial microenvironments. We will evaluate cell death, differentiation, morphology and division and specific signall ing pathways. We will collaborate to produce protocols to differentiate iPS cells into disease-relevant cell types. These approaches will provide in vitro readouts of inter-individual variation and disease and a platform for gene correction and engineering specific mutations into different genetic backgrounds. Our proposal will give researchers in the UK and beyond access to iPS cells and technology linked to extensive genetic, cellular and clinical information.
Development of a cytotopically-modified antithrombotic agent for prevention of acute intra-graft thrombosis in transplantation 01 Mar 2012
"Dr Richard Smith and Professor Anthony Darling of the MRC Centre for Transplantation at King's College London have received a Translation Award to develop a peptide-based anti-thrombin agent that is capable of rendering a transplanted organ resistant to thrombosis without using systemic anticoagulation . This is achieved by perfusing the organ with a membraneinteractive ("cytotopic") agent (which sticks to the organ vasculature) and then flushing out excess agent prior to transplantation. At least 25% of patients currently on the waiting list for renal transplantation are there because they have pre-existing antibodies against potential donor tissue. Attempts to transplant organs into such patients result in thrombosis within the organ which is difficult to treat with conventional anticoagulants and can lead to severe graft damage. The translation programme will refine processes for the manufacture of the lead cytotopic agent ("Thrombalexin') and will include safety studies to enable a firstin- man study in patients at high risk of intra-graft thrombosis following renal transplantation."
Planar cell polarity (PCP) orchestrates the coordinated orientation of cell structures within the plane of a tissue. In Drosophila, the asymmetric sub-cellular distribution of PCP components defines the position and alignment of epithelial structures. How specific distribution of vertebrate PCP proteins impacts on their role(s) during the complex morphogenesis that shapes embryo development is less well understood. Celsr1/Flamingo is a PCP signalling component capable of homophilic interaction w hose bipolar distribution at lateral membranes directs E-cadherin and planar cell divisions along the mammalian anterior-posterior (A-P) axis. This proposal has three goals. Firstly, to determine whether the recently reported distribution of Celsr1 to the basal membrane of neuroepithelial cells is polarised along the A-P axis of the vertebrate hindbrain and directs the tangential migration of cranial neurons via interaction with known basal membrane adhesion components. Secondly, to determine wh ether vertebrate PCP proteins such as Scribble, a known apico-basal determinant in Drosophila, influence how Celsr1 protein becomes localised in different epithelia. Thirdly, to map the structures within Celsr1 which drive the differential localisation of specific Celsr1 proteins. These studies will elucidate the fundamental importance of differential Celsr1 protein distribution and how apico-basal and planar polarities intersect to organise vertebrate morphogenesis.
Is the medial temporal lobe functionality heterogeneous for familiarity and recollection. 03 Mar 2011
We will recruit 90 hypoxic patients complaining of memory problems, from whom 60 participants will be selected on the basis of recall and/or item recognition memory impairments with damage confined to the medial temporal lobes. MRI measures of regional brain volumes in key structures, fibre tract integrity (DTI) and cerebral blood flow (CBF) will be obtained. Patients will be grouped on the basis of whether their damage primarily involves the hippocampus, perirhinal cortex, parahippocampal corte x, or more widespread medial temporal lobe volume loss. Several procedures will be used for measuring recollection and familiarity memory for different kinds of information, including structural equation modelling, in these patients and healthy controls. We will explore recollection and familiarity both for rapidly learned post-morbid memories and for frequently rehearsed, pre-morbid memories. These studies will be complemented by functional MRI (fMRI) investigations. By combining detailed analy sis of memory performance and brain imaging data, we will elucidate the extent to which the hippocampus, perirhinal cortex and parahippocampal cortex have differing roles in the recollection and familiarity of premorbid and post-morbidly acquired memories involving different kinds of information. More specifically, we seek to resolve the long-standing dispute about the role of the hippocampus in familiarity and recollection.
Novel approaches to quantitation and speciation of plasma non-transferrin bound iron: implications for prevention of iron mediated toxicity. 12 Oct 2010
In iron overload, the distribution to tissues at risk of iron toxicity is mediated though plasma species collectively referred to as non-transferrin bound iron (NTBI) but its nature has thus far been poorly characterised. The research will apply two novel analytical methods for the quantification and speciation plasma NTBI, developed by the principle applicant, to address key unresolved clinically relevant questions. NTBI speciation will be compared in iron overload conditions with different e xtra-hepatic iron distribution profiles, in particular with different iron loading to the myocardium. The relative effects on NTBI speciation of the currently used iron chelation (desferrioxamine, deferiprone, deferasirox) will be observed. The uptake of plasma NTBI species from plasma samples of patients into target tissues using hepatocyte and cardiomyocyte cell lines will be investigated by measuring intracellular iron fluxes fluorimetrically. The relative propensity of albumin bound and c itrate-coordinated NTBI species to uptake into these tissues will be determined, as well as the effects of clinically used chelators on this process. We hypothesise that albumin bound NTBI species will be more difficult to remove using chelation therapy than iron:citrate species. We further hypothesise that clearance of albumin bound NTBI species will occur more in hepatocytes than in myocardial cells.
Functional and structural thalamocortical connectivity after preterm birth and its relation to later cognitive abilities. 20 Jun 2011
Prematurity is common and increasing, and over one third of survivors have significant cognitive deficits. Preterm infants display widespread but poorly understood MRI abnormalities in thalamus, cortex and white matter which predict later cognitive abilities at 2 and 6 years of age. These develop before term during the period of maximal growth in thalamocortical connections which are required for normal cortical development, suggesting the hypothesis that: cognitive impairment in preterm infants is, at least in part, due to abnormal thalamocortical connectivity. I plan to address two questions: first, how does the thalamocortical unit develop from 26 to 44 weeks gestational age, quantifying the relation of functional and structural connectivity in a cross sectional MRI dataset; and second, is cognitive ability at 2 years of age predicted by structural and/or functional connectivity of the thalamocortical unit at term corrected age, using 832 datasets acquired in a large ongoing tri al. Using novel neuroinformatic techniques including new brain atlases, probabilistic tractography and resting state fMRI I will first examine thalamocortical connectivity for all major lobes and then focus on 26 regions in the temporal lobe. This will illuminate the development of human thalamocortical connectivity and may define new biomarkers for therapeutic intervention studies.
Legal and Ethical Aspects of Post-Trial Access to Trial Drugs, Health Care and Information. 19 Mar 2009
The ethics and oversight/regulation of PTA are of great and increasing social significance, particularly as a growing proportion of clinical research, which primarily benefits resource-rich countries, is conducted in resource-poor countries. Legislation/guidance is inconsistent, ambiguous or silent about many aspects of PTA. Criticisms of the demanding stance of the influential Declaration of Helsinki (2000) has generated a contentious revision (2008). PTA has many stake-holders with strong and often conflicting interests; some (commercial sponsors) are more powerful than others (e.g. participants in resource-poor countries). The various ethical/legal/practical arguments generated by research stake-holders have not been collected systematically and have received little scrutiny. Research Ethics Committees (RECs) may be unprepared to evaluate plans regarding PTA in the protocols that they review; this may be costly for sponsors, researchers, participants and society. I will draw on my background in philosophy, social science and research governance and work with experts to: collect the arguments for/against moral obligations regarding PTA; develop an informed/even-handed view; build a database of PTA legislation/regulations/guidance to donate to UNESCO s global, open-access database; conduct a comparative legal analysis; propose any necessary reforms; and develop guidelines in collaboration with the UK s National Research Ethics Service to enable RECs to assess PTA plans.
Mounting evidence indicates that the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD) result from failed immunological tolerance towards gut microbes, leading to chronic T cell-mediated inflammation. Interactions between T-cells and dendritic cells (DCs) are undoubtedly critical regulators of gut inflammation. We have recently reported a preclinical model of colitis where selective absence of the transcription factor T-bet in DCs results in spontaneous, TNF-alp ha dependent colitis with striking similarities to human UC. The question addressed by this study is whether these preclinical mechanistic pathways are relevant and translatable to human disease. We will define T-bet expression in lamina propria DCs from IBD patients and controls and determine its relationship to intracellular TNF-alpha expression. Using multicolour flow cytometry we will simultaneously define the phenotypes of DCs, T-cells and NK-cells, with respect to cell surface, intracell ular cytokine and transcription factors at an individual cell level. Using cutting edge phosphoflow analyses we will determine the role of transcription factor phosphorylation in conferring an inflammatory phenotype to these cell populations. We will manipulate T-bet expression in DCs to determine whether this alters their co-stimulatory capacity or influences their ability to drive effector T-cell function towards an inflammatory or regulatory phenotype.
Cognitive ageing in women: A twin study to identify determinants and imaging correlates. 04 Dec 2008
Cognitive decline with age is the most feared aspect of growing old (1). Ageing after 50years is associated with changes in cognitive function in the normal population, especially fluid abilities, like working memory, speed of processing and reaction time. Maintenance of these abilities as we age contributes to preservation of autonomy, independence and quality of life, and was described as one of three factors essential for successful aging (2). Cognitive ageing will constitute an incre asing challenge as life expectancy lengthens. Understanding the causal factors and physiological mechanisms leading to differential cognitive change within the normal population in later life is a priority. It is important to identify potentially modifiable factors contributing to successful ageing. This study uses a unique cohort of older twins with a large amount of longitudinal phenotypic data. It aims to identify the environmental factors contributing to 10-year cognitive changes among st female twins over 50 at first testing. It will then examine the extent to which cognitive change with age correlates with age related change in other organ systems. Lastly, it will examine the links between brain structural, functional and connectivity changes on MRI, and age related change in cognition, in mono-zygotic twins discordant for cognitive change.
Retrograde signaling in the central processes of primary sensory neurons: the influence of activity in the central nervous system on gene expression in peripheral neurons. 15 Jul 2008
Neuropathic pain caused by damage to the peripheral nerve has proved difficult to manage clinically. In part this is because research has implicated plasticity in both peripheral neurons and central pathways. We propose that neuropathic pain following peripheral nerve damage is maintained by a direct action of descending spinal pathways on both dorsal horn neurons and primary afferent fibers terminating within the dorsal horn. Our hypothesis is in two parts. First, that investigating molecular changes in the dorsal horn following manipulation of the descending pathways will uncover novel targets for the treatment of chronic pain conditions and second, that there is a two-way communication between the peripheral nerve and the central nervous system and that central neuronal changes drive long-term molecular changes in subsets of primary afferents thus increasing their sensitivity and maintaining the painful neuropathy. We therefore i) aim to identify gene transcripts in the dorsal horn and dorsal root ganglion that are regulated following central manipulations of descending pathways, ii) investigate retrograde signaling in dorsal roots, particularly CREB and CREB2, and their modulation by central processes.
i) To use a lentiviral vector system to deliver shRNA to sensory neurons in vitro and in vivo, and to specifically disrupt target gene expression. (ii) To use viral vectors to study the involvement of particular proteins in pain pathways and elucidate the mechanisms by which these proteins contribute to chronic pain states (iii) To improve the lentiviral vector system by enhancing its target cell specificity by, for example, modifying the promoter driving the shRNA expression
Cognitive processes in the maintenance and treatment of posttraumatic stress disorder and social phobia. 16 Sep 2008
The proposed research aims: 1) to improve understanding of the factors involved in maintaining post-traumatic stress disorder and social phobia, and 2) to develop more effective and efficient psychological interventions for these disorders. An integrated programme of prospective longitudinal studies, experiments, treatment development studies, and randomised controlled trials is proposed. A cognitive model of the maintenance of each disorder is outlined. The longitudinal and experimental studies investigate maintaining factors specified in the models. In posttraumatic stress disorder, the proposed maintaining factors include: excessively negative appraisals o the trauma and its sequelae (including the initial PTSD symptoms); data-driven processing and lack of self-referential processing; a characteristic autobiographical memory disturbance; and problematic behavioural and cognitive strategies that are used to reduce current distress but have the long-term effect of maintaining the disorder. In social phobia, the proposed maintaining factors include: using internal information (especially observer-perspective images) to make excessively negative inferences about how one appears to others; safety behaviours; and negative biased post-event rumination. In both disorders, the information obtained from the longitudinal and experimental studies, from recent pilot work, and from planned analyses of treatment tapes, is used to develop and refine cognitive therapy programmes that specifically target the maintaining processes. The new, more efficient programmes include a one week intensive treatment for PTSD and a self-study augmented programme for social phobia. The effectiveness of the cognitive therapy programmes is assessed in two randomised controlled trials. The overall strategy proposed for investigating the two disorders is one that has proved successful in the applicants' current programme grant.
Financial incentive schemes may be more effective than existing approaches in achieving the behaviour change needed for smoking cessation and weight loss. Yet such schemes elicit strong opposition in the media and among the general public, being variously described as unfair , a reward for bad behaviour , and coercive and manipulative . We aim to describewhich characteristics of incentive schemes make them more or less acceptable to the general population, as well as explore the motivations behind judgements of acceptability, such as concern for negative consequences, protected values, judgements of responsibility, and emotions such as disgust or anger. We further aim to disentangle factors which we hypothesize to influence the perception that incentives can sometimes be coercive or manipulative, and to establish the relationship between these judgements and those of acceptability.
The subventricular zone (SVZ) is one of the largest sources of neural progenitor cells in the adult brain. These cells migrate from the SVZ following a very precise route, the rostral migratory stream (RMS), to reach the olfactory bulb. Importantly, the adult SVZ responds to insults by producing new progenitors that migrate to sites affected by neurodegenerative pathology or injury. However, still remarkably little is known about the molecular mechanisms controlling neural progenitor migration. Our aim is to identify and characterise regulators of neural progenitor migration. We have identified a set of candidate key molecules with a microarray screen performed by inhibiting neural stem cell migration. In addition, our preliminary data point to a role in neural progenitor migration for the cannabinoid system and for Ral GTPases, regulators of cell cytoskeleton and membrane traffic. The role of our candidate molecules will be tested in established in vitro migration assays using neur al stem cell lines and SVZ-derived neural progenitors nucleofected with targeting small interfering RNA, or expressing wild-type and mutant versions of proteins of interest. The most interesting candidates will then be functionally tested in vivo by lentiviral vector-mediated RNAi or overexpression in mouse SVZ-derived neuroblasts labelled with GFP.