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Recipients:
University College London
Amounts:
£500 - £1,000
£1,000,000 - £10,000,000
Award Year:
2008

Results

Higher resolution cardiovascular epidemiology: unique insights from linking the national cardiac event register with primary care records and highly phenotyped cohorts. 16 Jul 2008

Background Our understanding of the aetiology of coronary disease in populations has been limited by low resolution in three key dimensions: phenotyping different coronary syndromes, the timing and evolution of risk, and the interplay between different risk factor domains. This uncertainty motivates each of our aims: Aim I Curation of novel research platform We will establish, validate and curate for the wider research community new, internationally unique, large-scale resources based on link ing the national myocardial infarction register to the rich longitudinal primary care record and highly phenotyped cohorts in the UCL genetics consortium. We will focus on stable angina, unstable angina, non-STEMI and STEMI (about 146,000 linked cases). Aim II Research To what extent are risk factors for specific chronic or acute coronary syndromes different from those of undifferentiated coronary disease aggregates? Across short and long-term risk periods, in aetiologic and prognostic set tings, we will address major aetiological domains including: social and psychosocial factors, physical environment, inflammation, biological markers and genetics. Aim III Training and education We will develop, deliver and evaluate new training opportunities at short course, MSc and PhD level to spawn a new cadre of academics trained in exploiting multiple sources of EPR for health research.

Amount: £1,159,056
Funder: The Wellcome Trust
Recipient: University College London

Population Science of Maternal and Child Survival. 14 Apr 2008

Since 1990, in sub-Saharan Africa and many populations in south Asia, there has been almost no progress with Millennium Development Goal (MDG) 5 to improve maternal survival, and a plateauing in the decline in under five mortality rates (MDG 4). Neonatal mortality rates remain stubbornly high. This strategic award programme has three objectives. Building upon existing trials, it will develop a global network of linked epidemiological surveillance sites in Bangladesh, India, Malawi and Nepal to study maternal and child health and survival in high mortality populations. The award will strengthen our network capacity to conduct meta-analyses and cross-country comparisons of data, especially for maternal mortality, to improve understanding of coverage, access and equity of uptake of maternal and newborn care, to collect longitudinal cohort data on growth and development among children, and to analyse linkages between health outcomes and proximate indicators such as poverty, social capita l and the strength of local health systems. Second the award will strengthen capacity to translate research evidence into policy and practice in partner countries and through international agencies. Third, it will strengthen capacity of partner institutions to design, manage and communicate high quality policy-relevant research, especially through south-to-south dialogue and peer-learning.

Amount: £5,496,183
Funder: The Wellcome Trust
Recipient: University College London

The National Survey of Sexual Attitudes and Lifestyles 2010 (Natsal 2010). 15 May 2008

As requested, to ensure that both the Wellcome Trust and the MRC have the same information, the summaries submitted to the MRC have been uploaded (Document 4).

Amount: £2,000,000
Funder: The Wellcome Trust
Recipient: University College London

Genome-wide association studies in partial epilepsies. 12 Jan 2008

scientifically qualified assessors (no more than 200 words): Genome-wide association studies (GWAS) are daily advancing understanding across human diseases, with enormous potential for disease prevention, generation of novel treatments and better use of existing treatments. We propose contemporary, potent GWAS to reveal genetic contributions to specific phenotypes in the partial epilepsies, which are the most common epilepsy type, representing the bulk of disease burden. We have already undertaken extensive genomics research. Experience, including our own, has enabled formulation of a successful strategy which we intend to apply to our multinational patient cohort collection established through an international collaborative consortium in epilepsy genomics. Our collaboration includes industry, with samples from GlaxoSmithKline collection, and funding contribution from GSK contingent on successful funding of the application. For this application, we have assembled a large cohort of well-characterised patients with partial epilepsy, secured access to even more patients, and established and applied consortium-wide definitions for disease and seizure types. Our published genotyping, association and post-association follow-up strategies, validating both our cohorts and our general approach, will be applied. Our key goals are to identify common genetic risk factors for disease susceptibility and seizure generalisation in the partial epilepsies and to generate a large genotype dataset for further studies.

Amount: £1,375,065
Funder: The Wellcome Trust
Recipient: University College London

Determinants of physical activity in the UK Millennium Cohort Study 06 Feb 2008

We will measure physical activity using accelerometers at age 7 and again at age 9 in the ethnically diverse UK Millennium Cohort Study and, in a random sample, establish how activity varies by season of year by measuring activity on three further occasions, each a season apart. Two calibration studies will be carried out in 7 and 9 year olds to determine cut-offs defining moderate and vigorous physical activity (MVPA). We hypothesise that MVPA will be inversely related to fat mass, but that th is may vary according to sex and ethnic group. We will test the following hypotheses: that children who are physically active have lower fat mass and less central fat; that children who are overweight or obese by school age are less active at primary school; that more active children have higher subsequent self esteem; that children who skip breakfast, drink sugary drinks or eat high energy snacks have higher fat mass and more centrally distributed fat at age 7; and that Body Mass Index is a no t reliable indicator of fat mass at this age.

Amount: £1,297,375
Funder: The Wellcome Trust
Recipient: University College London

Principles of neurotransmitter signal formation in the brain. 09 Apr 2008

Memories are formed trough use-dependent modification of synaptic circuits of the brain. Establishing the cellular basis of such modification, in health and disease, remains a fundamental challenge in neurobiology. Our aim is to elucidate mechanisms through which presynaptic mechanisms and the synaptic environment control formation of fast neurotransmitter signals at central synapses. We are proposing a multi-disciplinary investigation focused on individual excitatory synapses and their microenv ironment in the hippocampal circuitry. Our main research objectives include: - to determine mechanisms through which electrotonic signal propagation and target cell-specific actions of presynaptic kainate receptors affect transmission in the mossy fibre circuitry; - to establish the involvement of glia in use-dependent modifications of glutamatergic signalling; - to determine how the extracellular environment affects diffusion of fast neurotransmitters; - to elucidate presyna ptic mechanisms underlying fluctuations in the release probability and to evaluate the amount of glutamate released by a single synaptic vesicle. The study will capitalise on the existing experimental basis combining single-cell electrophysiology with state-of-the-art multi-photon microscopy techniques and extensive biophysical modelling. The project will also benefit from the first-class research environment and from collaboration with several groups leading in their areas of expertise.

Amount: £1,069,248
Funder: The Wellcome Trust
Recipient: University College London
Amount: £1,666,630
Funder: The Wellcome Trust
Recipient: University College London

The neural basis of spatial and episodic memory in humans. 09 Apr 2008

A distributed set of brain regions supports episodic memory, the memory for personal experiences. This brain network overlaps considerably with that associated with navigation and imagination. Surprisingly little is understood about the contributions individual brain areas within this network make in subserving these vital yet distinct cognitive functions. The goal of my research is to understand how these common brain areas, and possibly common processes, underpin episodic memory, navigation an d imagination. To examine this I will study healthy subjects and patients with non-progressive pathologies using fMRI and neuropsychological testing. As well as commonalities I will investigate differences, exploring which additional brain regions are co-opted into this common network to support operations unique to specific functions such as episodic memory. I will complement this systems level approach with a focussed examination of a key region within the common brain network, namely the hip pocampus, as damage to it has the greatest impact on the memory system. I will seek to establish what kind of information it represents using new high resolution imaging and multivariate decoding techniques. I believe that functionally deconstructing the memory system in this way will provide novel and fundamental insights into the mechanisms involved in coding our experiences.

Amount: £1,037,451
Funder: The Wellcome Trust
Recipient: University College London

Development and standardization of biologically realistic neural network models through an open source database. 08 Oct 2008

Models of neural networks in the brain are important for understanding how complex patterns of neuronal activity are generated by low level cellular mechanisms and network connectivity. They will be key for elucidating how information is processed in health and disease. Unfortunately, access to network models has been limited to a small group of computational neuroscientists with specialized programming skills. In this project we will build a database of high quality biologically realistic neura l network models that are accessible to a wide range of neuroscientists. This will involve developing new software tools and standardized model descriptions to facilitate the construction, modification, visualization and running of network models without the need to write code for specialized simulators. We will create an open source database (OpenSourceBrain.org) where collaborators, expert in a brain region, can actively develop models. Standardized model descriptions (NeuroML format) will pro vide a common language ensuring interoperability of model components and simulator independence. We will develop 3D models of the cerebellum and cortex with a high degree of biological realism through a close collaboration of theoreticians and experimentalists. Models will be tested thoroughly as part of research investigations and made freely available together with associated software tools.

Amount: £1,048,732
Funder: The Wellcome Trust
Recipient: University College London

TARP regulation of neuronal and glial calcium-permeable AMPARs in health and disease . 08 Oct 2008

The proposed programme aims to elucidate the roles played by TARPs in regulating CP-AMPARs during cell (neuron and glial) signalling and in certain important neurological disorders. We have four specific goals: (1) to determine the contribution of TARPs to a form of synaptic plasticity involving dynamic regulation of CP-AMPARs [functional studies patch-clamp techniques applied to cerebellar stellate cells in slices] (2) to elucidate fundamental mechanisms by which TARPs interact with , and control, functional properties of native and recombinant CP-AMPARs [patch-clamp recording from recombinant and native AMPARs, combined with calcium measurements and molecular biology] (3) to assess the role of TARPs in subcellular targeting and mobility of CP-AMPARs [immunocytochemistry and quantum dot-based tracking] (4) to investigate the role of TARPs in specific neurological conditions (affecting neurons and glia) where changes in the regulation of CP-AMPARs are implicated in di sease aetiology [patch-clamp methods, calcium imaging, immunocytochemistry and molecular biology in mouse models and glial-derived tumor cells]

Amount: £1,127,351
Funder: The Wellcome Trust
Recipient: University College London

The World Health Organization and the social determinants of health: assessing theory, policy and practice (an international conference). 29 Aug 2008

The World Health Oraganisation and the Social Determinants of Health: Assessing theory, policy and practice (An international conference).

Amount: £850
Funder: The Wellcome Trust
Recipient: University College London

No time for panic: British responses to influenza in peace and war, 1889-1919 29 Aug 2008

The 1918 influenza pandemic represents the worst outbreak of infectious disease in Britain in modern times. Although the virus swept the world in three waves between March 1918 and April 1919, in Britain the majority of the estimated 228,000 fatalities occurred in the autumn of 1918. In London alone deaths at the peak of the epidemic were 55.5 per 1,000- the highest since the 1849 cholera epidemic. Yet in the capital as in other great cities and towns throughout Britain, there was none of the panic that had accompanied earlier 19th century outbreaks of infectious disease at the heart of urban populations. Instead, the British response to the 'Spanish Lady' as the pandemic strain of flu was familiarly known was remarkably sanguine. As The Times commented at the height of the pandemic: 'Never since the Black Death has such a plague swept over the face of the world, [and] never, perhaps, has a plague been more stoically accepted.' The apparent absence of marked social responses to the 1918 influenza is a phenomenon much remarked on in the literature of the pandemic, as is the apparent paradox that despite the widespread morbidity and high mortality the pandemic had little apparent impact on public institutions and left few traces in public memory. However, to date no one has explored the deeper cultural 'narratives' that informed and conditioned these responses. Was Britain really a more stoical and robust nation in 1918, or was the absence of medical and other social responses a reflection of the particular social and political conditions that prevailed in Britain during the First World War and then medical nosologies and cultural perceptions of influenza? And if the 1918 pandemic was 'overshadowed,' as one writer puts it, by the war and the peace that followed the Armistice, what explains the similarly muted response to the Russian flu pandemic of the early 1890's, a disease outbreak that coincided with a long period of peace and stability in Britain? In this project I aim to show that, contrary to previous studies, both the 1918 and the 1889-92 Russian flu pandemic were the objects of much deeper public concern and anxiety than has previously been acknowledged and that the morbidity of prominent members of British society, coupled with the high mortality, occasioned widespread 'dread' and in some cases alarm. However, in 1918 at least, government departments and public institutions actively suppressed these concerns for the sake of the war effort and the maintenance of national morale.

Amount: £657
Funder: The Wellcome Trust
Recipient: University College London