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Recipients:
University College London
Amounts:
£500 - £1,000
£1,000,000 - £10,000,000
Award Year:
2007

Results

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

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

Epigenomics of common disease. 31 Aug 2007

The major histocompatibility complex (MHC) and leukocyte receptor complex (LRC) are the two most polymorphic immune loci in the human genome. Both are associated with multiple disease pathologies including most if not all autoimmune diseases. As part of the MHC and LRC Haplotype projects, we have generated the only multi-Mb single haplotype sequences in the human genome, comprehensive gene and variation maps, high-resolution (1.6 kb) and population-specific linkage disequilibrium maps and a first generation of MHC and HLA allele tag SNPs. Building on this existing resource, the following projects are proposed: (1) MHC Haplotype Project, (2) HLA tagSNPs; (3) Reconstructio of the ancestral MHC haplotype sequence in Europeans; (4) LREC Haplotype Project, and (5) Identification of MHC/LRC tans-acting variants.

Amount: £1,051,000
Funder: The Wellcome Trust
Recipient: University College London

Neuroesthetics. 12 Sep 2007

The development of powerful techniques for imaging brain activity has ushered in an interest in the neurobiology underlying artistic creativity and aesthetic appreciation, in fields as diverse as art, literature, music and mathematics. The new field of neuroesthetics studies these subjects and relies on contributions both from neurobiology and the humanities. This application aims to promote the study of neuroesthetics in the UK, where the concept was born. The main goal is to produce world clas s research addressing issues that have long been debated in the humanities concerning the nature of art and beauty, the relationship of both to the atavistic impulses of love, and the role of reward, judgment, affective states, knowledge and concepts in the creation and appreciation of works of art. Other goals are to train future generations of researchers to tap knowledge acquired in the humanities to develop questions amenable to scientific experimentation; to educate undergraduate students a nd the public about the relevance of neurobiological studies to issues of concern to science and society. Finally, it will provide a framework within which to unite the apparently disparate fields of neurobiology and the humanities in the common pursuit of understanding the human brain and the human condition.

Amount: £1,128,963
Funder: The Wellcome Trust
Recipient: University College London

UCL Gene Therapy Vector Production. 19 Sep 2007

Our aim is to develop cost-effective, sustainable, state-of-the-art adeno-associated and lentivirus vector production for clinical gene therapy trials and subsequently treatments. This will be achieved by: 1. Recruitment and training of a Director, Administrator and Production Team. 2. The supply to UCL academic investigators of small batches of clinical grade vectors and transduced cells for Phase I/II clinical studies from existing GMP laboratories at UCL. 3. Ongoing development and updati ng of vectors and production processes, both from UCL innovations and by the adoption of international best practice. 4. Using the pump-priming provided by a Wellcome Biomedical Resource Award to develop a self-sustainable, larger vector production facility. This will supply academic investigators and health care providers in the UK and internationally with vectors on a not-for-profit basis.

Amount: £1,765,881
Funder: The Wellcome Trust
Recipient: University College London

Structure function models of language and its recovery. 26 Jun 2007

My proposal is to establish a functional anatomical model of language that predicts how speech and reading are lost and recovered following neurological damage. The novel aspect of this model rests on my hypothesis that distinct language tasks can be sustained by several different neuronal systems. Crucially, this means that when one system dysfunctions, recovery can be meditated by a surviving system. The neuronal systems engaged by each task will be identified by combining data from neuropsych ological and functional imaging studies. Validating the model involves structural neuroimaging and behavioural assessments in patients with acquired brain damage in the regions identified. This will determine how the impact of damage in one system depends on the integrity of another. The model will then be used to formulate and test predictions for recovery using functional imaging studies of patients who recover their language skills despite damage to the areas engaged by normal subjects. The ability to anticipate which brain systems emerge, during rehabilitation, may be important for targeting various therapies or, at least, in helping the patient anticipate his or her course of recovery.

Amount: £1,275,779
Funder: The Wellcome Trust
Recipient: University College London

Decoding consciousness. 07 Jun 2007

Currently the best way of discovering whether someone is having conscious experiences is to ask them, which is sometimes impractical or impossible. The ultimate goal of the proposed research is to establish biomarkers of consciousness that circumvent this need. I will flexibly combine non-invasive imaging technologies (fMRI & MEG) with new methodological approaches (high spatial resolution imaging and multivariate pattern recognition) to examine what distinguishes conscious and unconscious repre sentations in the human visual pathways, both cortical and subcortical, for both patients with focal cortical damage and healthy volunteers. I will further examine the potential causal role of frontal and parietal structures (plus cortico-cortical or thalamocortical coupling) in awareness, using TMS and fMRI either alone or in combination. Clinically, changing the level of consciousness causes profound effects on the ability of neural representations to reach awareness. I will therefore study ho w sensory representations change in patients undergoing anaesthesia using intraoperative fMRI. Finally, I will bring together all of this work in attempting to dynamically decode both conscious perception and intention from brain activity alone. The prospect ultimately afforded by this work is the ability to decode consciousness in humans (and possibly animals) for health and human benefit.

Amount: £1,038,457
Funder: The Wellcome Trust
Recipient: University College London

Defining the role of primary cilia in development and disease. 07 Jun 2007

The primary cilium is enjoying renewed interest having been ascribed sensory roles and more recently associated with regulation of aspects of development. We discovered the debilitating Bardet-Biedl syndrome (BBS) arises from ciliary dysfunction. Our recent data implicate BBS proteins in cell polarisation (PCP) and sonic hedgehog (Hh) transduction potentially linking the processes via their role in intraflagellar transport (IFT). We aim to identify the precise point of action of BBS proteins in relation to PCP and Hh signalling. We stand to gain insights into fundamental biological processes and understand why they produce certain phenotypes when disrupted. BBS is one of an emerging new group of disorders, the ciliopathies. Through comparisons with BBS, we predicted other ciliopathies such as the often lethal, Jeune syndrome (JS). By specifically searching out ciliary genes we identified the first JS gene (IFT80), the protein for which is directly involved in IFT. We aim to investigat e function of Ift80 by generating a conditional mouse knockout and studying different aspects of organ involvement. Finally, we will extend our preliminary observations of rapamycin rescue of renal cysts in bbs and ift80 morphant zebrafish to Bbs mutant mice (which also develop kidney cysts) paving the way for human trials.

Amount: £1,530,307
Funder: The Wellcome Trust
Recipient: University College London

Nitric oxide signalling in the CNS. 06 Feb 2007

Nitric oxide (NO) serves as a diffusible signalling molecule throughout the CNS. Despite progress, there remains a poor level of understanding about how this atypical messenger functions and this is the focus of the research proposal. To address the lack of knowledge of physiological or pathological NO signals (e.g. their amplitude, duration and spread) we have designed novel NO biosensors capable of registering physiological NO concentrations (predicted to be subnanomolar) and propose to use th em to record NO formation from all the relevant sources in the CNS, namely from neuronal, endothelial and inducible NO synthases. The second aim is to analyze NO signal transduction through its guanylyl cyclase-coupled receptors in a quantitative manner. To do so, we have designed a new technique capable of recording receptor function in real time. Together, these first two components offer the hope of generating a quantitative description of NO signalling comparable to that existing for the maj or neurotransmitters. The third goal relates to NO-cGMP signal transduction in the brain. Building on recent unexpected findings, the hypothesis under investigation is that endogenous NO acts on neurones to regulate (through cGMP) hyperpolarization-activated, cyclic nucleotide-gated ion channels.

Amount: £1,220,044
Funder: The Wellcome Trust
Recipient: University College London

The molecular mechanisms of activation of G-protein gated inwardly rectifying K+ channels 22 Feb 2007

The hypothesis I would like to examine is "In atrial myocytes the inhibitory G-protein subunit nucleates the formation of a signalling complex of a dimeric G-protein coupled receptor (GPCR), for example the M2 muscarinic receptor, heterotrimeric G-protein, regulators of G-protein signalling and G-protein gated K+ channel." Specifically the goals are Goal 1:- To examine for M2 muscarinic, A1 adenosine and S1P3 sphingosine-1-phosphate receptor dimerisation and to delineate the molecular determinants and consequences of oligomerisation in native atrial myocytes. Goal 2:- To determine if a complex exists of GPCR with Gi\o-protein heterotrimers and with GIRK channels prior to agonist exposure and what happens to the complex in the presence of agonist. Goal 3:- To examine the role of individual Gi\o isoforms and RGSs, in particular RGS3, RGS4 and RGS5, in signalling to GIRK channels in native atrial myocytes.

Amount: £1,039,333
Funder: The Wellcome Trust
Recipient: University College London

Genomic and biochemical analysis of ageing and age-related disease. 18 Jul 2007

A recent discovery is that mutations in single genes can extend healthy lifespan in laboratory organisms. Furthermore, these effects are conserved over large evolutionary distances, opening the opportunity to use simpler organisms with much shorter lifespans to understand human ageing. Mutations in insulin/IGF-like signalling (IIS) genes can extend lifespan in the worm Caenorhabditis elegans, the fruit fly Drosophila and the mouse. Our collaborative research programme has three aims: 1. Our previous work has both demonstrated robust conservation of the effects of IIS on lifespan in Drosophila and produced a new, robustly long-lived mutant mouse. We shall unravel the signalling mechanisms involved, essential for identification of possible drug targets. 2. We shall identify and manipulate the biochemical processes by which IIS slows ageing, the key to understanding how ageing-related damage is generated and how normal longevity is assured by defence and repair systems. We shall focus on detoxification, autophagy and the proteasome. 3. Ageing is the major risk factor for predominant, lethal diseases: cardiovascular disease, cancer and neurodegenerative disease. We shall test the idea that ageing-related diseases are caused by the same accumulation of molecular damage that drives the ageing process, focussing upon neurodegenerative diseases in the model organisms and humans.

Amount: £5,127,323
Funder: The Wellcome Trust
Recipient: University College London