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Funders:
Paul Hamlyn Foundation
The Wellcome Trust
Recipients:
University College London
Amounts:
£500 - £1,000
Award Year:
2008

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Results

Value in people award. 21 Oct 2008

Not available

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

Southern Africa Consortium for Research Excellence (SACORE) 17 Dec 2008

The key goals of SACORE are to develop and sustain a critical mass of local research scientists to be independent investigators and leaders capable of attracting competitive research grants. To achieve this we plan to improve research management and support capacity, introduce undergraduates to research, and stimulate research outputs at all levels of the research career pathway. This will be achieved through a number of interventions within the southern Africa region: 1. Developing south-south and strengthening existing north-south networks, through annual scientific meetings, mentorship, and joint PhD supervision. 2. Developing research leadership through mentorship of mid-level and senior scientists and by conducting relevant leadership and training courses. 3. Building a critical mass of research scientists, and research career pathways for them, through: a. competitive WT-SACORE PhD scholarships. b. competitive WT-SACORE post-doctoral fellowships. c. competitive WT-SACORE MSc scholarships d. providing competitive small research grants e. providing focus workshops to enhance research skills. 4. Consolidating career progression using professional development planning for all staff. 5. Establishing and strengthening Research Support Centres in the three low-income institutions including the provision of appropriate staff, equipment and skills and developing appropriate research governance and support frameworks. Importantly, the RSCs will pro-actively encourage and support scientists in their grant applications.

Amount: £55,056
Funder: The Wellcome Trust
Recipient: University College London

Bugs R Us 01 Oct 2008

The "Bugs R Us" project has been devised to bring the excitement of new developments in microbiology to as wide an audience as possible through a travelling exhibition with a 5-year shelf-life. Human beings are a symbiotic association of mammalian and microbial cells with the latter (the indigenous microbiota) outnumbering the former by a factor of ten. The indigenous microbiota is hugely diverse and consists of more than 2,000 different species which are organised into a variety of communities whose composition varies with the anatomical site. Although some species are able to cause disease, our microbial symbionts collectively exert a number of beneficial effects. Hence they protect us against pathogens, provide up to 10% of our energy requirements, supply a range of vitamins and play a key role in the development of our immune system and mucosal surfaces. Few people are aware of the importance of our indigenous microbiota and, because the populist view is "all microbes are dangerous and must be eliminated", it is important that this unwarranted view of microbes is corrected. By using modern exhibition techniques, talks and seminars we intend to: (i) introduce to the general public the concept that a human being is a symbiosis of mammalian and microbial cells (ii) provide new insights into the nature of the microbial communities that reside on our bodies, (iii) explain how the anatomical site governs the composition of the microbial community residing there (iv) describe what benefits these microbial communities confer on humans.

Amount: £29,375
Funder: The Wellcome Trust
Recipient: University College London

InBodied. 01 Oct 2008

Artist and performer Catherine Long will collaborate with neuroscientists Professor Patrick Haggard and DR Beatriz Calvo-Merino, and dance/choreographer Frank Bock on research centred around embodiment and the relationship between brain and body. I will study the tension between the subjective and objective experience of the body, and the mechanics of the body, based on my unique physicality. The project will culminate in a performance (work in progress) involving movement, sound and video. This will address perceptions of and through the typical or atypical body, and the body's role in subjective experience. There will also be an exhibition of photographs and a short film will be made.

Amount: £30,000
Funder: The Wellcome Trust
Recipient: University College London

Pattern Completion 01 Oct 2008

The project brings together a neuroscientist, an artist and a sound designer to create an installation exploring how networks of brain cells recall memories. Audio-visual sequences will be projected onto a suspended spiral of glass spheres. Initially the images and sounds will be hard to decipher, but as time passes they become increasingly coherent, following a theoretical process known as pattern completion. The installation will invite the audience to consider how their brain pieces together a memory and the implications this has for how our memories are structured.

Amount: £29,929
Funder: The Wellcome Trust
Recipient: University College London

The Point of Perception. 01 Oct 2008

This project explores the area of ambiguity in perception, which is inherent in the artworks of Madeleine Boyd and fundamental to the research of neuroscientists Mark Lythgoe and Beau Lotto. The practice-based research nature of this project will provide a frame work for both artistic and scientific partners to develop their own work as well as producing work together. A series of scientifically driven events based around Boyd's sculptural environments will allow the collaborators to generate a genuinely interdisciplinary methodology. The series culminates with an exhibition, catalogue and discussion day, all aimed at reaching targeted audiences effectively.

Amount: £28,960
Funder: The Wellcome Trust
Recipient: University College London

Control of Attention in the human brain studied with real-time fMRI. 04 Dec 2008

Many forms of brain damage, either acute or progressive, can compromise patients ability to move and to communicate. While much work has focused on attempts to reverse the pathological process causing such damage, rather less has sought to provide complementary approaches of circumventing the effects of damage by using brain signals from sensory or motor cortex to control neuroprosthetic devices. Moreover, investigating the neural basis of such signals has direct biological relevance for unders tanding mechanisms of perception and action. Here, I propose to use the new technique of real-time fMRI (rt-fMRI) to address both issues. My proposal thus addresses two inter-related questions of biological and practical significance. First, can attention be decoded in real time from human visual cortex to potentially provide control signals for a neural prosthesis? Second, does the level of attentionally modulated activity in human visual cortex have a causal influence on perception and awarene ss? I will combine real-time functional MRI (rt-fMRI) with on-line neurofeedback in human participants in a series of experiments that both probe the effects of attention on visual cortex and evaluate the potential utility of decoding such signals for communication and control.

Amount: £189,768
Funder: The Wellcome Trust
Recipient: University College London

Cone photoreceptor rescue in inherited retinal degenerations. 04 Dec 2008

This project is to investigate whether slowing cone photoreceptor loss could be used as a widely applicable treatment to preserve sight in inherited retinal degenerations. Neurotrophic factors, apoptosis inhibitors and transplanted rods have previously shown promise, but key questions remain: 1. Are initial rescue effects maintained over time, or subsequently lost by accelerated apoptosis? 2. Can cone cell rescue still be achieved once all rods have degenerated (a common clinical scenario)? 3. Could rods transplanted into the vitreous slow cone degeneration (the vitreous is a clinically attractive site for cell transplantation)? These questions will be addressed using adeno-associated viral (AAV) gene transfer to achieve sustained intraocular levels of a promising neurotrophic factor with a clinical safety profile (GDNF - delivered to inner retinal cells by AAV serotype 2) and cone selective expression of a potent intracellular inhibitor of apoptosis (XIAP - delivered to photo receptors by AAV serotype 5). In the third experiment rod progenitors will be isolated and transplanted into the vitreous cavity. All experiments will be performed in a novel mouse model of rod-cone degeneration in which the cones are genetically labelled with a fluorescent probe, allowing repeated anatomical and functional tracking of the degeneration over time.

Amount: £179,898
Funder: The Wellcome Trust
Recipient: University College London

REGULATION OF THE ANTIOXIDANT STATUS OF ENDOTHELIAL CELLS BY MITOCHONDRIA AND AMP-ACTIVATED PROTEIN KINASE ALPHA 1. 15 Oct 2008

We propose to investigate the way in which nitric oxide (NO) contributes to the maintenance of the antioxidant status of vascular endothelial cells. To do this we intend to: 1) study the signalling cascade initiated by the generation of mitochondrial reactive oxygen species (ROS) as a result of the interaction of NO with cytochrome c oxidase at 3% O2; 2) identify the role of AMPK (in particular the catalytic alpha 1 subunit) and redox-responsive transcription factors (e.g. Nrf2, FOXO) in this pathway; 3) explore whether this system maintains a constitutive defensive state in these cells which, if impaired, removes their protection against potentially pathophysiological situations, such as hypoxia and oxidative stress, that occur in conditions such as diabetes or metabolic syndrome.

Amount: £190,078
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

Population coding of natural sounds in the mammalian auditory system. 09 Dec 2008

Despite the recent advances in our understanding of sensory function, the neural representation of complex natural stimuli remains a mystery. This gap in our understanding can be attributed to two complex properties of sensory systems that are important under natural conditions, but are not addressed in typical laboratory experiments involving recordings of the responses of a single neuron to simple stimuli: (1) the response properties of sensory neurons are not static, but are constantly adapte d to match the current statistical properties of the stimulus and (2) the representation of complex stimuli is not confined to the response of a single neuron, but is distributed across the responses of an interconnected population. I plan to study these complex properties in the inferior colliculus (IC) of the auditory midbrain. I will record the responses of small populations of neurons simultaneously during the presentation of natural stimuli and characterize the response properties of these neurons using a variety of system identification and information theoretic techniques. I will also use these experimental results to develop a model that incorporates the effects of adaptation and population interconnectivity in predicting neural responses to natural sounds.

Amount: £691,979
Funder: The Wellcome Trust
Recipient: University College London

A machine learning approach to the analysis of psychiatric neuroimaging data. 09 Dec 2008

The World Health Organization (WHO) states that one in four people experience a mental health problem during their life. The development of technologies for assisting psychiatric diagnosis and predicting treatment responses is extremely relevant to avoid inefficient treatment and to promote mental health. The purpose of this research is to develop models and tools for the application of novel machine learning techniques to the analysis of brain scan data to assist in the understanding, diagnosis and prognosis of psychiatric disorders. Key Goals: 1. Development of new machine learning techniques for the analysis of brain scans including: - Probabilistic classifiers to predict group membership (e.g. patients vs. controls and - responders vs. non-responders); - Hypothesis-driven models of brain alterations in psychiatric disorders (e.g. schizophrenia, depression); - New strategies to extract useful information from neuroimaging data (i.e. feature selection approaches). 2. Developme nt of multi-modal classification integrating data from different techniques (e.g. fMRI, MRI, EEG, genetic data). 3. Validation of the developed approaches using a variety of data sets. 4. Translation of the validated approaches into clinical practice, i.e. development of a toolbox that could be used for aid diagnosis of psychiatric disorders and other clinical/outcome goals.

Amount: £619,620
Funder: The Wellcome Trust
Recipient: University College London

The role of Sox2/SOX2 in hypothalamo-pituitary development. 08 Oct 2008

The overall aim of this project is to understand better the role of the transcription factor SOX2 in normal hypothalamo-pituitary development and in the pathogenesis of hypopituitarism in humans. Recently, we have identified a critical role for the transcription factor SOX2 in normal hypothalamo-pituitary development in both mice and humans; however, the molecular mechanism by which SOX2 dictates hypothalamo-pituitary development, namely its target genes and partner proteins, remains unknown. Th e main aims of the proposed research are: 1. To evaluate the ability of SOX2 to directly regulate specific genes known to be involved in forebrain and hypothalamo-pituitary development, and to identify the positions of these genes in the genetic hierarchy leading to normal pituitary development. 2. Identification of novel SOX2 target genes likely to be important in hypothalamo-pituitary development. 3. To investigate suitable co-operative partner factors for SOX2 in the developing pitu itary and their co-expression in human embryos. 4. Selection of candidates for mutation analysis of novel SOX2 target genes in patients with hypopituitarism and associated defects.

Amount: £359,039
Funder: The Wellcome Trust
Recipient: University College London

Endoglin regulates angiogenesis: an investigation of cellular and molecular mechanisms. 10 Nov 2008

Development and maintenance of an optimally functioning vasculature are essential for health. Abnormal vessel responses can result in a range of vascular problems including haemorrhage, vessel dilatation or aneurysm, which may be associated with increased morbidity and mortality, depending on the affected organ. The aim of this project is to understand the role of the essential endothelial receptor endoglin during development of the vasculature. Pathological mutations of the endoglin gene in the familial vascular disorder Hereditary Haemorrhagic Telangiectasia lead to the local formation of arteriovenous malformations and haemorrhagic, dilated and tortuous blood vessels (telangiectases) that often enlarge or become more numerous with age. The molecular mechanisms underlying these events are poorly understood, largely because of a lack of robust animal models. We have recently derived an inducible endoglin knockout mouse which, for the first time, develops arteriovenous malformations in a reproducible manner. We will use this unique model to investigate the underlying cellular and molecular mechanisms responsible for abnormal vascular remodelling. Following this, we aim to investigate repair of these vascular abnormalities. Increased understanding of the central role of endoglin in angiogenesis has wider implications for current therapies to regulate angiogenesis and vascular repair in an extensive range of pathologies.

Amount: £105,970
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 UK National Juvenile Dermatomyositis cohort : genotype/phenotype studies, and their application to mechanisms, clinical course and outcomes. 15 Oct 2008

This application is to request funding of a cohort of children with myositis, now one of the largest of its type in the world, that can make a major international contribution to the field. The cohort comprises clinical data linked to biological samples (serum, plasma, DNA, PBMC and muscle biopsy tissue), contributed from a Network of centres across the UK (see Appendix1). Standardised clinical data are collected using validated, internationally agreed, robust, clinical tools. Data and samples f rom several years are available, allowing studies of response to treatment, biomarker and candidate gene discovery, including genotype/phenotype correlations, and long-term disease outcomes. The resource is managed by an independent Steering committee, with patient involvement, and is available to the scientific community through an open application process. The resource is much in demand from UK and International researchers; several research projects are planned and funded. For this resource t o survive, the core needs include an Administrator, a Research Assistant, and running costs. A key objective of this proposal is to further develop availability and visibility of the resource through a website, making it more accessible to the wider scientific community, allowing information and data generated to make a larger impact upon health outcomes.

Amount: £279,790
Funder: The Wellcome Trust
Recipient: University College London

Transthyretin depletion for treatment of hereditary systemic and senile cardiac amyloidosis 19 Dec 2008

Systemic transthyretin amyloidosis is a fatal late onset disease caused by tissue deposition of amyloid fibrils composed of variant and wild type transthyretin. The objective of the project is to construct compounds to trigger the accelerated clearance of plasma transthyretin molecules by the liver by synthesising palindromic ligand-linker-ligand compounds capable of cross-linking transthyretin molecules or oligosaccharide-ligand conjugates that direct hepatic clearance, which could be used as drugs for treating and preventing acquired and hereditary human systemic transthyretin amyloidosis. The aim is to optmise the design, synthesis, and properties of a transthyretin depleting drug and complete the comprehensive safety and efficacy evaluation required prior to administration of a validated candidate compound in humans.

Amount: £610,617
Funder: The Wellcome Trust
Recipient: University College London

Neurogenesis in the mouse telencephalon. 21 Oct 2008

The molecular mechanisms regulating neuronal development in the telencephalon are largely unknown. The aims of the project are twofold: (1) examine the role of the transcription factor NKX2.1 in immature postmitotic neurons of the telencephalon and (2) identify genes involved in the development of neuronal populations in the embryonic subcortical telencephalon.

Amount: £34,720
Funder: The Wellcome Trust
Recipient: University College London

Properties of oligodendrocyte precursor cells. 21 Oct 2008

This project will investigate the properties of oligodendrocyte precursor cells, examining in particular their response to neurotransmitters, their voltage-gated currents, their role in myelination, their developmental fate and their effects on nearby neurons.

Amount: £12,700
Funder: The Wellcome Trust
Recipient: University College London