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University College London

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Object Retrieval. 18 Mar 2009

Object Retrieval is an exciting 8 month interdisciplinary project culminating in a highly innovative week-long performative event. In this event a massive team of researchers from across UCL's science, social science and arts faculties will explore the 'biography' of one object from UCL's remarkable but undervalued Pathology Collection. This real-time research will creatively demonstrate the synergistic benefits of interdisciplinary research through unravelling an object usually situated exclusively within a medical context. Open to the public, Object Retrieval, led by artist Joshua Sofaer highlights the increasingly cross-disciplinary nature of biomedical research in a 21 century university and will bring welcome attention to the pathology collection. A multi-media wiki will accompany the project and ensure an enduring legacy, along with a limited edition artwork/resource pack for teaching.

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

History of Medicine MA dissertations. To be held at the Wellcome Trust Centre for the History of Medicine on 16 May 2009 21 Apr 2009

The intention of the meeting is to foster collaboration in History of Medicine MA programmes in the UK and Ireland through establishing joint training days. The meeting will enable students from such programmes to make short presentations of their MA dissertations, and to interact with and get feedback from their peers from other programmes, as well from tutors from other departments. The aim of the meeting is to establish a centralised platform for the training of History of Medicine MA students suitable for generic research skills. The most critical research component of the current programmes is the dissertation, which for a number of students, forms a point of departure for a subsequent History of Medicine Phd. The aim of the meeting is to better prepare students for their MA dissertations and for continuing research in the history of medicine.

Amount: £2,300
Funder: The Wellcome Trust
Recipient: University College London

"History of Medicine in Motion" to be held at UCL on 26 May 2009. 21 Apr 2009

This workshop is intended to involve researchers in the methods for creating video clips about the History of Medicine. These clips are intended to present scholarly research either in public contexts, at academic conferences or to students in the classroom. During the workshop participants will receive feedback on video clips that they have developed, and prizes will be awarded to the best submissions. The final roundtable session, consisting of senior scholars in the History of Medicine from Harvard and UCL a major Israeli filmmaker from the National Television and Film School, and staff from the Wellcome Library will critically appraise this media as a vehicle for communicating scholarly research. The project will be web-based, all clips available to the public on the internet; furthermore, the conference proceedings will be live-streamed during the event itself.

Amount: £5,000
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

Assessing the challenges faced by health systems in providing paediatric Cotrimoxazole prophylaxis in resource limited countries. 16 Sep 2008

HIV exposed infants are 16 times more likely to die in their second six months of life than unexposed infants, largely due to respiratory infections. Cotrimoxazole prophylaxis significantly reduces both mortality and morbidity. In Zimbabwe it is estimated that only 11% of exposed infants are prescribed cotrimoxazole and the extent to which it is correctly taken is unknown. The aim of the project is to describe the process and obstacles to provision of cotrimoxazole prophylaxis for HIV exposed infants in three sites in Zimbabwe, focusing on issues related to drug supply and adherence. This information will be used to develop an evidence-based intervention for improving its provision. The study will be conducted in three phases in two Zimbabwean health centres, one urban, one rural: 1) guidelines and standard operating procedures for PMTCT, cotrimoxazole prophylaxis and aftercare of HIV infected mothers will be studied; 2) implementation activities at study clinics including identification of HIV infected mothers, procedures for ensuring babies are prescribed cotrimoxazole and adhere to treatment will be assessed as will aftercare for HIV positive mothers; 3) the findings will be disseminated to stakeholders to identify solutions and develop an evidence based intervention relevant for Zimbabwe and the wider region

Amount: £73,801
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

Open Access Award. 16 Sep 2008

Not available

Amount: £40,000
Funder: The Wellcome Trust
Recipient: University College London

Inhibitory processes in human voluntary action. 17 Apr 2008

The phenomenon of the conscious intention to act is an elusive but interesting aspect of cognition. Actions can be classified as being either stimulus driven or voluntary (Goldberg, 1985). In this context, stimulus driven actions are those that are done in response to an external stimulus. This external stimulus, through an association however arbitrary, unequivocally specifies the movement to be done. Voluntary actions, on the other hand, do not appear to be elicited by any obvious external stimulus. Instead, they arise as a result of the integration of many different sources of information. (Cunnington et al., 2002, Haggard, 2008). According to one recent model, three main components characterise voluntary action (Brass and Haggard, 2008). These are decisions regarding not only the identity (what) and the timing (when) of the action, plus a final check that allows withholding a prepared action (whether decision). This final ?veto? or Intentional Inhibition (II) would be important not only as a self-control mechanism, but also in situations where the task environment has changed. As actions are planned with some anticipation, it is reasonable to expect an online checking mechanism to be advantageous for flexible and appropriate behaviour. Experimental paradigms designed to address voluntary action are very often subject to criticism. Because experiments should be reproducible and interpretable, they tend to be simple, artificial in nature and of a low ecological value (Libet et al., 1983, Haggard and Eimer, 1999, Lafargue and Duffau, 2008). A genuine ?urge? to perform an action is hard to generate in the laboratory environment. Objective methods for studying intentions and convincing measures of the subjective experience of intention are thus relatively scarce. Increasing interest has arisen in the potential mechanisms for II, but in order to experimentally address II, one needs to achieve four things: - generate the urge to perform a movement, - induce participants to prepare to make the movement - allow them to choose to refrain from doing the movement at the very last moment, and - have an appropriate measure of this inhibition. By definition, there is no behavioural outcome to this kind of paradigm. Despite this methodological problem, some experimental paradigms have yielded robust results. Brass and Haggard (2007) asked participants to prepare a button press and to inhibit the prepared action in some trials. They have shown the selective activation of a brain area, associated with an endogenous cancellation function. An area of the anterior frontomedian cortex (dFMC), rostral to the presupplementary motor area (preSMA), was activated more when subjects had to cancel a prepared action than when they carried on with it. We propose to develop a more naturalistic and physiologically plausible paradigm for intentional inhibition, based on inhibiting the urge to scratch following electrically induced itch. In this proposed paradigm, although the urge to move is driven by a specific itch stimulus, the inhibition of the scratching is self-generated, and related to the urge to scratch. This combination therefore represents a significant improvement to the traditional paradigms of II used thus far.

Amount: £148,655
Funder: The Wellcome Trust
Recipient: University College London

Interaction of Decision-making and Action Planning in the Human Brain. 17 Apr 2008

The current project aims at a more detailed understanding of how the brain translates decisions into actions. Traditionally, decision-making and action planning are considered (and studied) as separate processes that occur largely independently, with brain processes leading to a decision required to precede those involved in planning the resulting action [1,2]. Recent evidence suggests that in a large number of cases, decision-making occurs in an action-dependent way, sharing common neural resources with action selection [3-6]. For example, decision-related neural signals can be observed in areas traditionally assigned to ?motor processes? (e.g. superior colliculus: [7]; frontal eye field: [8]; premotor cortex: [9]. In the human brain, the interplay between decision-making and action planning remains to be determined. In particular, it remains is unclear (1) whether different systems subserve decisions that are related or unrelated to specific actions [10], and (2) how different decision variables influence and enter the motor system when the decision is linked to a particular action. The proposal addresses these timely questions, using a combination of non-invasive neuroimaging, electrophysiological recording, and neurostimulation techniques in healthy human adults.

Amount: £148,655
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

Mechanisms of social interaction. 16 Sep 2008

While I am already supported by the Wellcome Trust, my position is currently as a component of the grant awarded to Richard Frackowiak. On the basis of past career and current work it is more appropriate for me to have independent funding. The work I plan will generate a substantial series of linked experiments in a number of cognitive domains. I anticipate that much of the day to day work will be carried out by a series of research fellows and PhD students. Long-term funding for the coordinator of this group is essential to provide continuity and coherence across these projects and to ensure an optimum environment for the training of a new generation of clinical neuroscientists. In addition, a long-term view is needed to ensure that the work of my group continues to feed into and benefit from developments in the other groups that compose the Functional Imaging Laboratory. Functional imaging techniques, particularly fMRI, are going to change and develop rapidly over the next ten years. My past career demonstrates that I have the flexibility to learn and take advantage of new developments as they arise. Long-term funding will obviate the shot-term risks associated with the exploitation of these new developments. My fundamental aim is to increase understanding of brain abnormalities underlying psychosis. Of necessity this is a long-term goal since much work on normal brain function is needed before cognitive paradigms and brain imaging techniques can be applied to the study of psychosis. This work will span at least a ten year period.

Amount: £18,848
Funder: The Wellcome Trust
Recipient: University College London

Core support for the Wellcome Trust Centre for Neuroimaging. 12 Jul 2010

In seeking to renew the Wellcome Trust Centre for Neuroimaging (WTCN) we have developed a scientific strategy based on promoting diverse research themes that all rest on understanding brain function in terms of formal models. More specifically, our aim is to develop models that provide a generic framework for the analysis of in-vivo brain data that critically includes fMRI, MEG and EEG data (the principal modalities used by the Centre PI's), but also data acquired from direct human inter-crania l recordings and animal based local field potential data. Our aim is to furnish basic and clinical neuroscience with common, model based, frameworks capable of integrating findings from animal recordings through to patient studies. In this context our overarching goal is to extend the range and depth of the neuroscientific questions we address by promoting a scientific vision with sufficient maturity to tackle the most difficult problems in neuroscience, namely the breakdown in neuronal functi on that characterises common neurological and neuropsychiatric disorders.

Amount: £7,575,569
Funder: The Wellcome Trust
Recipient: University College London

Upgrade of MRI scanners at the Wellcome Trust Centre for Neuroimaging at UCL. 02 Jul 2009

Reliable and high-performance scanning facilities are integral to the future success of the Wellcome Trust Centre for Neuroimaging (WTCN). The current two MRI systems at the WTCN are reaching the end of their effective life-time and are not equipped with the latest advances in MRI technology. Consequently, cutting-edge neuroscience programs at the WTCN may soon be compromised unless we proceed with their replacement and upgrade. We have developed an upgrade strategy consisting of 2 phases. In p hase 1, over the next 12 months, we will replace the 1.5T Sonata whole-body scanner with the latest 3T hardware and will upgrade the 3T Allegra head scanner from 4 to 8 receive channels. In phase 2, implemented in 24-36 months, we will replace the 3T head scanner with the latest generation of hardware. Currently, we envisage a replacement with a 3T system but this phased programme keeps open an option for an upgrade to a 7T platform if considered appropriate on scientific grounds. The proposed u pgrade strategy will significantly improve the performance of the Centre's imaging platforms, maintain a diversified scanning infrastructure, and make novel imaging approaches more tractable, thereby securing the leadership of the Centre in applied imaging neuroscience.

Amount: £1,302,100
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

Development of a novel high throughput screen for cytoplasmic entry of cell penetrating peptides. 21 Jul 2009

In our opinion, none of the current methods for assessing uptake of proteins by CPPs are able to give a rapid, accurate, and quantitative measure of cytosolic uptake. Our aims are therefore: (i) Generation of a high throughput, quantitative assay for the transport of proteins into the cytoplasm of mammalian cells by cell penetrating constructs. Our proposed assay is based on monitoring the cytoplasmic cleavage of a GFP-derived FRET construct We assume that GFP, which does not adhere to nor penetrate mammalian cells, will serve as a good model for proteins as cargo for penetrating constructs. In particular, we will be focusing on viral entry peptide sequences as a basis for penetrating construct design. (ii) Identification of peptide sequences that promote facile release of the GFP construct from endosomes following endocytosis. We hope to identify general sequence motifs that will promote and assist with endosomal release of proteins. (iii) Detailed FRET study of the cell entry of bromomaleimide-derived CPP bioconjugates both at cellular and <ingle molecule resolution. (iv) In addition to the screening of CPPs to enable protein cargo delivery, we will also consider other penetrating constructs. Neocarzinostatin (NCS) is known to gain cell entry in a proficient manner and ultimately interact with nuclear DNA (Schaus et al. 2001 ). It is unclear, however, what the mechanism of NCS cell entry is and whether it is ever exposed to the cyloplasm. Our proposed methodology would provide an ideal platform on which to determine this. (v) Comparison of the cell surface stability of both bromomaleimide- and disulfide-derived FRET constructs. These experiments will give an insight into whether PDis or thioredoxins could inhibit the cell entry of disulfide-derived conjugates and whether bromomaleimide-linked conjugates offer an adv2ntage in this regard. (vi) Appliccation of optimised CPPs to the cell delivery of academically and/or therapeutically interesting protein targets. This research may be performed in collaboration with interested research groups or organisations.

Amount: £152,244
Funder: The Wellcome Trust
Recipient: University College London

Multimodal interactions in the human brain. 21 Apr 2009

The project will focus on two related scientific questions that seek to understand how the brain processes and relates information coming from different sensory modalities. First, what are the functions and mechanisms of multisensory interactions in the human brain? Second, what is the role of awareness in multimodal processing? I will investigate these questions using a combination of non-invasive neuroimaging approaches such as BOLD contrast fMRI and magnetoencephalography (MEG).

Amount: £152,990
Funder: The Wellcome Trust
Recipient: University College London

The computational neurobiology of attention. 21 Apr 2009

1. Work up a plausible model of behaviour in the task, based on the Free Energy Principle and informed by knowledge of cortical structure and neurotransmitter action. 2. Acquire performance and neuroimaging data in the task from normal subjects. Use these data to parameterise and optimize the model, using Bayesian model comparison. 3. Choose one or two psychoactive drugs that are implicated in mental disorder and abnormal task performance in normal subjects and measure performance on this task under these drugs. I will then re-parameterise the model for performance on this drug. The PhD will focus on attention. Patients with schizophrenia seem to be particularly deficient in attentional tasks which involve conflict or identifying which stimulus to attend to (Luck & Gold, 2008; Wang et al., 2005; Maruff et al., 1998). Thus, I will use a modified version of the Posner task (Posner et al., 1978), which introduces conflict, to study this phenomenon. In the Posner subjects are required to foveate a central spot and respond as quickly as possible to the appearance of a peripheral target. The side the target will appear is cued at a fixed interval beforehand. The cue is correct (valid) 80% of the time. Posner found that reaction times to validly cued targets were significantly shorter than to targets which were incorrectly cued. This demonstrated that attention could be moved to salient locations in the absence of gaze shift. Evidence as to the performance of schizophrenic patients in this task is mixed. The choice of this paradigm is based partly on the fact that the groundwork of the modelling has already been done. Moreover, the Posner paradigm yields a wealth of data ? the values parameterising the reaction time distributions to cues with up to three different levels of validity, plus the proportion of correct responses ? which will furnish empirical constraints on key model parameters (e.g., synaptic rate constants and gain). In addition, the cognitive processes engaged by this paradigm are clearly influenced by the pathological process underlying schizophrenia.

Amount: £152,990
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