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Recipients:
University College London
Currency:
GBP
Award Year:
2007

Results

Objective measurements of physical activity in primary school children in UK Millineum Cohort 19 Dec 2007

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 this 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 not reliable indicator of fat mass at this age.

Amount: £146,000
Funder: The Wellcome Trust
Recipient: University College London

Value in People Award. 17 Oct 2007

Not available

Amount: £350,000
Funder: The Wellcome Trust
Recipient: University College London

'PhD Training Programme in the History of Medicine' to be held at the Wellcome Centre for the History of Medicine at UCL from October 2007 to June 2008. 05 Oct 2007

Meeting: PhD Training Programme in the History of Medicine, Wellcome Trust Centre, UCL, London We propose to hold a series of one-day workshops as outlined below, to be jointly staffed by academics and administrators from Oxford Brookes university and the Wellcome Trust Centre for the History of Medicine at UCL. Since academics will give freely of their time, the Trust will gain a national training programme at considerably less cost than for other funding councils.

Amount: £5,400
Funder: The Wellcome Trust
Recipient: University College London

Socioeconomic determinants of disability in Eastern Europe. 04 Dec 2007

The proposed research will investigate the levels and predictors of disability in urban population samples in three Eastern European countries (Poland, Russia and the Czech Republic). The key scientific goals of the project are: (i) to provide estimates of the prevalence of disability in these populations; (ii) to analyse the association between disability and socioeconomic factors over the life course; (iii) to assess the relative importance of different socioeconomic factors; (iv) and to investigate whether differences in the prevalence of disability between populations can be explained by individual-level socioeconomic variables. An equally important goal is to provide the candidate with comprehensive training in epidemiology and in the area of ageing. The project will use data collected by the HAPIEE study, a large multi-centre study funded by the Wellcome Trust (the candidate is based in the Polish HAPIEE study centre). The baseline survey, completed in 2005, recruited more than 29,000 men and women aged 45-69; Wave II will be completed in 2008. Disability will be defined as impaired physical functioning and reduced ability to perform usual activities of daily life, and the covariates will include socioeconomic status in childhood and adulthood, current income and wealth.

Amount: £25,767
Funder: The Wellcome Trust
Recipient: University College London

Methods in Molecular Microbiology - A capacity development programme for Africa. 05 Oct 2007

This training programme will provide 15 attendees from across east Africa with: 1. Update on the basic princples of molecular biology 2. Introduction / update on the principle techniques of molecular biology in the context of infectious diseases. 3. Hands on experience of these techniques. 4. Specialist update lectures addressing current issues in clinical microbiology and viology. 5. Introduction to and hands on experience of bioinformatics. This short course provides an introduction or refresher to scientists and clinicians who by virtue of their age or career path have missed out on recent developments in the use of molecular tools in diagnosis and epidemiology of infections.

Amount: £21,310
Funder: The Wellcome Trust
Recipient: University College London

tRNA retrograde transport and HIV-1 nuclear trafficking: a surprising connection. 24 Oct 2007

We have recently discovered that cytoplasmic tRNAs can be transported back into the nucleus in human cells, a process called retrograde tRNA transport, and that this process is exploited by HIV-1 to infect non dividing cells. We hypothesize that specific cellular factors drive nuclear import of tRNAs in human cells and that HIV-1 nuclear import is also promoted by the same factors. We aim to investigate this by: 1) Isolating the cellular factors driving tRNA nuclear import by chromatographic an d genetic approaches. 2) Disrupting their function by stable knock down or generation of dominant-negative mutants and examine the impact on HIV-1 infection in dividing and non-dividing cells. 3) Mapping the viral determinants for incorporation of and interaction with tRNAs with nuclear import activity by the generation of HIV-1 and murine leukaemia virus (MLV) mutants.

Amount: £367,002
Funder: The Wellcome Trust
Recipient: University College London

The role of the mitochondrial endogenous inhibitor, IF-1, in ischaemia and reperfusion injury in the heart. 15 Oct 2007

Mitochondrial dysfunction is central to the pathogenesis of a number of major diseases. At the heart of this proposal is the principle that a decreased mitochondrial membrane potential causes the mitochondrial ATP synthase to operate in 'reverse', switching mitochondria from ATP producers to consumers. The best characterized example of this mechanism is the response of cardiac muscle to ischaemic injury, in which mitochondrial dysfunction defines the borderline between reversible and irreversibl e injury. ATPase activity is modulated by the endogenous inhibitor protein, IF-1, which should be protective by conserving cellular ATP at the expense of allowing the potential to dissipate. As ATP depletion and changes in mitochondrial membrane potential play key roles in defining the progression of ischaemic injury, understanding the processes by which they are regulated is key to understanding the progression of ischaemic injury and so defining therapeutic targets. The proposed experimental w ork will therefore explore the impact of overexpression or suppression (siRNA) of IF-1 protein levels on the evolution of ischaemic injury in cardiac cells and cell lines. Mitochondrial state also defines the pathways of cell death, and so the work will also identify the impact of IF-1 on cell fate.

Amount: £277,607
Funder: The Wellcome Trust
Recipient: University College London

Epidemiology and treatment of Epilepsy in sub-Saharan Africa. 04 Dec 2007

I plan to conduct cross sectional surveys in five demographic surveillance sites across sub-Saharan Africa, to identify cases of active convulsive epilepsy (ACE). This cohort will be used to determine the prevalence of ACE and the extent of the number of people not receiving treatment (treatmetn gap) in these sites, identify the causes (particularly parasitic diseases that could be prevented) and establish cohorts of people with epilepsy, from which the magnitude and causes of excess mortality a ssociated with epilepsy can be determined. In addition, a community based intervention will be tested through a randomised cluster trial in one of the sites, to reduce the treatment gap and improve the quality of life of people with epilepsy in this area.

Amount: £2,041,821
Funder: The Wellcome Trust
Recipient: University College London

Identification and characterization of novel regulators of mammalian cell morphogenesis using RNAi. 12 Dec 2007

Actin filaments form a dynamic skeleton beneath the plasma membrane of animal cells and are crucial for cell morphogenesis. As a result, defects in cytokeletal regulation contribute to a variety of human diseases. Until recently, however, efforts to identify the mammalian genes involved were limited by the difficulties of studying essential genes in whole animals, so the set of genes currently investigated are a biased group. But the sequencing of several animal genomes and the discovery of ds RNA-mediated interference (RNAi) has enabled unbiased screens to identify known and novel genes involved. In the past year, the Baum lab has used genomic information to generate a human siRNA library targeting all known conserved actin regulators, and they have performed a genome-wide RNAi screen in Drosophila cell culture for novel actin regulators. Here, I propose to use RNAi to perform a comparative functional analysis of the complete set of actin regulators in fly and mammalian cell culture. I will then characterize several novel genes that play a conserved role in the regulation of the actin cytoskeleton. This will be one of the first studies to use unbiased loss of function genetics to identify genes involved in the regulation of animal cell form.

Amount: £321,854
Funder: The Wellcome Trust
Recipient: University College London

What is the metric structure of the cognitive map? 10 Oct 2007

The study of how hippocampal place cells and entorhinal grid cells represent place largely underpins the cognitive neuroscience of navigation and memory. Previous studies, however, used unrealistic environments in the form of small, two-dimensional enclosures, whereas the real world has an extended, complex, three-dimensional (3-d) structure that complicates navigational processes like path integration. This project will study encoding of 3-d space by manipulating both suface elevation (using sl oped environments including a ramp and a helix) and movement through 3-d, volumetric space, to explore the questions of (1) whether planar place fields and grids are calibrated according to the environment's surface or to the horizontal plane, and (2) of whether in three dimensions, place fields are actually globular and grids are actually lattices in 3-d space. Some of these experiments will exploit newly emerging telemetric technology, which enables recording in spaces too complex for a teth ered animal to explore. The main hypothesis is that the vertical dimension is indeed encoded, but differently from the horizontal ones. The results will not only expand our understanding of the place representation but also shed light on human 3-d navigation processes in aviation, astronautics and undersea exploration, as well as design of artificial navigating agents.

Amount: £161,847
Funder: The Wellcome Trust
Recipient: University College London

A genomewide association study of refractive error in the 1958 British Birth Cohort. 18 Oct 2007

We propose a novel and timely two-stage genomewide association study of refractive error (RE) in a nationally representative population, the 1958 British Birth Cohort (1958BC). Our joint analysis approach will be informed by our recently completed lifecourse epidemiological investigation of environmental determinants [12] and our on-going candidate-gene association study [13], both within this population which provides unique opportunities for studying complex traits. Additional strengths inclu de: -our leadership of the ophthalmic component of the MRC-funded biomedical survey of the 1958BC at 44 years allowing primary myopia phenotype capture without misclassification -robust measurement of quantitative trait of RE in a random subsample (N=2093) -good power to detect modest effects (eg >80% power to detect alleles contributing 10% variance) with likelihood of false discovery within reasonable limits -the extant 1958BC DNA bank funded by Wellcome Trust -prior inclusion of a sub sample of 1958BC in the WT Case Control Consortium [14]. -existing resources for the staff costs of the present proposal -high-throughput high quality genotyping (Illumina s Infinium technology) outsourced to commercial organisations with whom we have established links Our proposal adds value to substantial prior investment in the 1958BC as a national resource for biomedical research, as well as in our work on RE.

Amount: £591,024
Funder: The Wellcome Trust
Recipient: University College London

The human visuomotor grasping circuit: distinct contribution of parietal and frontal areas and their interactions with the primary motor cortex. 10 Oct 2007

Object grasping and manipulation involve a complex parieto-frontal cortical network including the anterior intraparietal area (AIP), the ventral premotor cortex (PMv) and the primary motor cortex (M1). However, the precise operations performed by AIP and PMv and both their lateralization and temporal coupling are still unclear. In addition, how grasp-related information, processed in PMv, is conveyed to M1 to generate an appropriate motor command remains unknown. New methods of assessing activi ty and cortico-cortical connectivity in this visuomotor grasping circuit now make it possible to investigate (1) the nature and timing of the interactions between PMv and M1 to visually guided grasping movements (2) the distinct contributions of AIP and PMv to these movements and (3) how contralateral and ipsilateral cortical areas belonging to the visuomotor grasp circuit interact with each other. We propose to use a novel paired-pulse transcranial magnetic stimulation (TMS) to investigate th e functional connectivity between PMv and M1 during different categories of hand movements or action observation and to document the influence of AIP on these PMv-M1 connections. In addition, we will use magnetoencephalography (MEG) to study the lateralization and timing of those interactions to understand the spatio-temporal flow of grasp-related information within the visuomotor circuit.

Amount: £134,412
Funder: The Wellcome Trust
Recipient: University College London

The London Pain Consortium. 07 Nov 2007

Chronic pain is prevalent and its clinical treatment remains limited. The London Pain Consortium (LPC) will advance knowledge of chronic pain mechanisms through internationally competitive research and provide multidisciplinary training of clinical and biomedical scientists to promote careers in neurobiology in general and pain studies in particular. In man and animals, we will: 1) identify molecular and genetic influences on pain processes; 2) study the integrative functions of these influenc es and their translation as therapeutic targets; 3) provide research and training resources for the wider scientific community.

Amount: £1,522,432
Funder: The Wellcome Trust
Recipient: University College London

The consequences of temporal lobe epilepsy surgery . 10 Oct 2007

We will investigate the effects of temporal lobe epilepsy and surgical removal of the anterior temporal lobe on cognitive functions that involve the temporal and the frontal lobes, and mood. We will investigate the functional neuroanatomy of these processes and how the frontal and temporal lobes are interconnected in terms of function and the white matter tracts that provide structural connectivity. We will implement and evaluate methods to predict the effects of anterior temporal lobe resecti on on cognition, mood and the field of vision, and how to subsequently minimise these risks. We will advance the technology of tractography and its integration with anatomical imaging, and will use temporal lobe surgery as a test-bed to implement combined serial fMRI and tractography after cerebral insults to determine the basis of recovery and plasticity.

Amount: £1,487,687
Funder: The Wellcome Trust
Recipient: University College London

'The importance of medical history: Transnational and cross-cultural perspectives on a multi-faceted discipline' conference to be held in Mumbai, India from 15th to 17th November 2007. 17 Oct 2007

The importance of medical history: Trans-national and cross-cultural perspectives on a multi-faceted discipline The proposed meeting will be the first of its type in the South Asian sub-continent - dealing with the important questions of historical method and historiography, from trans-national and cross-disciplinary perspectives; it will allow the audience access to a plethora of perspectives on how to study HOM. The projected audience will be university and college teaching, research and administrative staff of all grades, we well as undergraduate and post-graduate students, doctors, print and TV journalists, and independent researchers. A number of well-known scholars have agreed to attend the meeting, as they acknowledge the usefulness of an event like this in popularising HOM in an important education centre in Asia. These academics, who are attached to a number of Wellcome Trust-funded units, will draw upon an important item of their research - dealing with Europe, North America, Asia and further afield - to develop trans-national perspectives of how to study HOM. This meeting will engender a lot of discussion, which is critically important for an endeavour that seeks to provide new insights to post-and under-graduate teachers about important international developments in the discipline, and the most effective ways of teaching and carrying out research. Themes to be covered: History of pharmacology; Anatomy; Global trade and medicine; Medical genetics and gender; Medicine in the early modern period; Public health in 19th and 20th centuries; Global health programmes and disease eradication; War and medicine; International perspectives on rabies; Scottish doctors and British empire; Obstetrics and surgery; Cross-disciplinary perspectives on leprosy and empire; Hospitals; Medicine and 'witchcraft' in the early modern period; Healthcare in colonial Mumbai/India; Health of industrial labour; Oral histories of contemporary medicine and biological science; History of medical practice and multiple meanings of health.

Amount: £600
Funder: The Wellcome Trust
Recipient: University College London

Distinguishing signal from noise in a sensory cortical network. 10 Oct 2007

Distinguishing signal from noise in a sensory cortical network One of the most intriguing questions in neuroscience is how networks of neurons in the mammalian brain work together to store information and thus allow learning to take place. This proposal will use in vivo electrophysiological experiments in rodent barrel cortex combined with theoretical work to understand several key questions related to neural coding in mammalian cortex. We will address the following key questions: Do networks use average spike rate to process information or is the precise timing of every spike important? Is the coding scheme modified by the state of the network, in particular by background noise? How many neurons are needed for accurate transmission of information?

Amount: £13,004
Funder: The Wellcome Trust
Recipient: University College London

Electrophysiological and imaging studies of hite mechanisms underlying brain white matter pathology. 10 Oct 2007

Electrophysiological and imaging studies of mechanisms underlying brain white matter pathology This project will investigate in depth the mechanisms leading to oligodendrocyte damage in pathological conditions, and some properties of oligodendrocyte precursor cells relevant to normal myelination during development and to remyelination in pathological conditions.

Amount: £5,430
Funder: The Wellcome Trust
Recipient: University College London

Hippocampal oscillations and synaptic plasticity - in vitro experiments and theoretical insights. 10 Oct 2007

Hippocampal oscillations and synaptic plasticity - in vitro experiments and theoretical insights To understand the mechanisms underlying the characteristic population firing patterns of pyramidal cells in the CA1 region, which are the principal output from the hippocampal formation. Achieving this goal will take into account the connectivity, synaptic kinetics and neuronal properties of the hippocampal formation, and emerging information on the different types of activity-dependent synaptic plasticity at distinct synapses in the elemental cortical microcircuit.

Amount: £10,755
Funder: The Wellcome Trust
Recipient: University College London

Transport and signalling of cell adhesion molecules and their role in motor neuro survival. 10 Oct 2007

We previously demonstrated that histone H2A is phosphorylated at Ser129 in response to DNA damage by the Mec1p and Tel1p kinases in yeast. Others demonstrated that the analogous residue in mammalian chromatin (Ser139 on histone H2AX) is also phosphorylated in response to DNA damage, and H2AX is a tumour suppressor gene in mice, demonstrating that this is a central event in eukaryotic DNA damage responses. Yet, it is still not entirely clear how this phosphorylation event functions to facilitate survival after DNA damage occurs. We therefore propose to further investigate the function of H2A phosphorylation using three approaches. First, we will systematically characterize the phosphorylation event by analyzing the timing, kinetics, and genetic dependence of phosphorylation in different cell cycle phases, growth phases and ploidy backgrounds. Second, we will examine the fate of phosphorylated H2A. Third, we plan to investigate the effect of phoshpoinositol signalling on H2A phosphorylation and DNA damage responses. Finally, we will integrate these studies with ongoing research in the lab in which we have identified proteins that bind specifically to phosphorylated H2A. Together, these studies will advance our understanding of this highly conserved event in particular and of DNA damage responses in general.

Amount: £35,635
Funder: The Wellcome Trust
Recipient: University College London

Modulation of axonal spike generation and propagation. 10 Oct 2007

Modulation of axonal spike generation and propagation Axonal action potentials are the main output signal of neurons and the basis for neuronal computation and signalling. Although regarded as all-or-non reaction, the propagation and shape of the action potential is modulated and dependent on axonal properties like diameter and ion channel composition. The aim of the project is to investigate the influence of axonal ion channels which are modulated by neurotransmitters (KCNQ, GABAA) on the propagation of the action potential in Purkinje cells of the cerebellum.

Amount: £9,637
Funder: The Wellcome Trust
Recipient: University College London