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Current Filters

Recipients:
University College London
Award Year:
2016

Results

Africa Health Research Institute (USD record) 30 Jun 2016

Our aim is to reduce the huge burden of HIV and TB in KwaZulu-Natal as a precursor to the eradication of these diseases. This will be facilitated by merging the population based research excellence of the Wellcome Trust (WT)-funded Africa Centre (AC), with the cutting edge laboratory science and experimental medicine approaches of the Howard Hughes Medical Institute (HHMI)- funded KwaZulu-Natal Institute for Research in TB and HIV (K-RITH) to create an exciting, interdisciplinary South African based research initiative. Our 5-year vision is to use basic science, systems biology, health systems and social science research to undertake fundamental discoveries into the susceptibility, transmission and cure of HIV and TB. Our specific questions are: 1. How can new HIV infections best be eliminated? 2. How can TB transmission be interrupted and how can drug-resistance be contained? 3. How can the health of pregnant women with HIV and their offspring be improved? 4. How can we improve the health-system delivery and population-level impact of HIV treatment and other chronic disease care? 5. How is health and wellbeing affected by migration, economic and other inequalities

Amount: £25,602,371
Funder: The Wellcome Trust
Recipient: University College London

Understanding cellular organisation: from archaea to eukaryotes 05 Jul 2016

We know surprisingly little about the basic logic, topology or origins of eukaryotic cell architecture even though such an understanding is fundamental to most biomedical research. Until recently, the proteins responsible for shaping eukaryotic cells (including Actin/Tubulin/coatamers/ESCRTIII) were thought to be unique to eukaryotes. This changed with the discovery of close homologues in TACK/Loki-family archaea. Despite the important part played by these proteins during eukaryogenesis, we know little about their functions in the context of archaea. To determine how these cytoskeletal systems with origins in archaea contributed to the emergence of internal compartments that define eukaryotes, our team will use metagenomic sampling and phylogenomics to trace their evolutionary history, and a combination of approaches, including live super-resolution microscopy and electron tomography to carry out a comparative analysis of their ultrastructure, dynamics and function in both archaea and eukaryotes. Ultimately, we expect this evolutionary cell biological analysis to make a start towards an understanding of archaeal cell biology, to reveal the likely path of eukaryogenesis, and to reveal underlying principles of eukaryotic cell biology that so far have eluded us. In doing so, we expect this fundamental research to have a signficant impact in the future on human health and disease.

Amount: £1,122,019
Funder: The Wellcome Trust
Recipient: University College London

Created Out of Mind: Shaping perceptions of dementia through art and science 07 Mar 2016

Created Out of Mind will shape public and professional perceptions of dementia through a dynamic fusion of scientific and creative experimentation. Our Hub residency will support the active connection and collaboration of previously disparate cultures (scientists, artists, commissioners/policymakers) and infuse the insights and skills of people living with dementia, communications professionals and collaboration experts. Common (mis-)conceptions of dementia will be challenged through integrated artistic and scientific investigation of less recognised symptoms associated with typical and rare dementias. The project will investigate the neuroscientific, artistic and social bases of artistic engagement, enjoyment and change across multiple art forms. Interdisciplinary discussion, disagreement and creativity will also challenge and develop thinking regarding the principles, priorities, practice, health benefits and methodologically-robust evaluation of arts in dementia. Our inspiration comes directly from the intriguing experiences, heart-rending questions and puzzling uncertainties of people living with dementia. Team members will become creative collaborators whilst maintaining their professional ‘essence’, yielding a richly and meaningfully interconnected network of multi-skilled science/arts researchers, practitioners and communicators. We will also enrich understanding about dementia by raising provocative questions about the healthy brain, our emotional reactions to change in ourselves and others, and the attributes by which we value and define humanity.

Amount: £715,199
Funder: The Wellcome Trust
Recipient: University College London
Amount: £12,000
Funder: The Wellcome Trust
Recipient: University College London

UCL - Neuroscience 30 Sep 2016

Not available

Amount: £133,252
Funder: The Wellcome Trust
Recipient: University College London

University College London/Birkbeck Interdisciplinary Programme in Structural, Computational and Chemical Biology 30 Sep 2016

University College London/Birkbeck Interdisciplinary Programme in Structural, Computational and Chemical Biology

Amount: £133,252
Funder: The Wellcome Trust
Recipient: University College London

University College London/Birkbeck Interdisciplinary Programme in Structural, Computational and Chemical Biology 30 Sep 2016

University College London/Birkbeck Interdisciplinary Programme in Structural, Computational and Chemical Biology

Amount: £133,252
Funder: The Wellcome Trust
Recipient: University College London

Life history of an organizer: what determins transient orgnaizer function in Hensen's node? 30 Sep 2016

The "primary organizer" of the vertebrate embryo is a group of cells at the gastrula stage which is able to induce a complete patterned nervous system when transplanted to another site. However, the position in the embryo where the organizer is located only has these properties for a short time. This time corresponds to when two particular populations of cells ("central epiblast" and "posterior deep") come together. After this, as cells leave to form the prechordal mesendoderm, organizer ability is lost again. The aim of this project is to find out whether the organizer function of Hensen's node is the sum of properties that exist in separate cell populations or whether new properties are generated by interactions between them, and thus determine how dynamics of these cells contribute to the transient nature of organizer function. Cell dynamics will be studied using carbocyanine dye (Dil and DiO) labelling of the 'central' and 'posterior' populations to identify their contributions and roles in the organizer. These populations, individually and combined, will be assessed by studying their transcriptomes by RNA sequencing. Their organizer function will then be assessed, in time-course, by the gene expression profiles in cells receiving signals from these populations

Amount: £28,350
Funder: The Wellcome Trust
Recipient: University College London

The role of the blood nerve barrier in peripheral neuropathies. 30 Sep 2016

The nervous system in maintained in a protective environment by a specialised vasculature. In contrast to the Blood Brain Barrier (BBB), the Blood Nerve Barrier (BNB) is poorly characterised despite having an important role in protecting peripheral nerves and its disruption being associated with neuropathies associated with pathologies such as diabetes and cancer. We have initiated a characterisation of the BNB in the sciatic nerve and have found that it is distinct from the BBB both in its permeability and cellular make-up. Moreover, we have developed a unique transgenic mouse in which ERK signalling in Schwann cells (SCs) in the nerve can reversibly open the barrier, which mimics the normal injury response. This provides a powerful model system for studying in a temporal manner how the BNB can be broken down and reformed. The aims of this proposal are threefold. 1. To characterise the nature of the BNB throughout the PNS and correlate differences with structural changes 2. To determine the role of SC-secreted Semaphorin 3A in the regulation of the BNB. 3. To analyse the expression and role of BBB transporters in the BNB.

Amount: £34,680
Funder: The Wellcome Trust
Recipient: University College London

Probing the synaptic mechanisms of human genetic neurological disorders 30 Sep 2016

We are interested in how mutations that lead to human neurological disorders (particularly epilepsy) impact neuronal function. Much of our previous work has focused on how mutations change intrinsic neuronal excitability, but epilepsy is increasingly being associated with genes which are also predicted to perturb synaptic activity, and the aim of this project is to probe whether a subset of mutations linked to similar genetic epilepsy disorders have similar consequences for pre-synaptic properties. We will develop a lentiviral tool that will express a fluorescent protein (e.g. RFP) and a cDNA or shRNA to mimic a genetic disorder in a subset of cultured neurons. Recordings will be from untransduced post-synaptic cells, limiting the possibility of post-synaptic genetic effects contaminating readouts of the impact of mutations on synaptic release. We will also investigate whether incorporation of an activating opsin is sufficient for light based stimulation of the pre-synaptic neurons only. By incorporating cellspecific promoters, this project will also allow us to test the hypothesis that mutations that cause seizures have distinct effects in interneurons and excitatory neurons, including how they couple excitation to transmitter release. This project will dissect the synaptic mechanisms of disease, and correlate them with subsets of neurons.

Amount: £5,805
Funder: The Wellcome Trust
Recipient: University College London

Understanding within-patient Mycobacterium tuberculosis genetic diversity to prevent drug-resistance 29 Jun 2016

Tuberculosis, caused by Mycobacterium tuberculosis (M.tb), is a major public health problem. Drug-resistant tuberculosis (DR-TB) cases are increasing, creating a significant barrier to disease control. DR-TB is difficult to diagnose and treatment often takes years. M.tb was traditionally thought to be genetically homogenous within the human host, but deep whole genome sequencing (WGS) data have revealed evidence of within-host genetic heterogeneity (GH), particularly in drug-resistance genes. Changing GH patterns over time can cause acquired drug-resistance (ADR). However, how and where in the host GH arises, or how important it is for ADR is not known. I hypothesise that GH represents isolated M.tb subpopulations in separate lung lesions within a patient, and that development of GH is related to local pathology or drug penetration. I will investigate this by WGS of M.tb extracted from resected human lung tissue, and comparing GH to pathology type and local drug concentrations. To evaluate whether GH causes ADR, I will follow patients with newly diagnosed MDR-TB and perform WGS of sequential sputum samples over 6 months for WGS. I will evaluate if ADR is related to baseline GH. Understanding the role of GH in ADR could help develop prevention strategies.

Amount: £380,125
Funder: The Wellcome Trust
Recipient: University College London

Understanding and predicting prognosis for adults with depression 02 Mar 2016

Depression is the most burdensome disease world-wide in terms of years of life lost to disability. Approximately 90% of depressed patients receiving psychological therapies in the UK are treated in Improving Access to Psychological Therapies (IAPT) services. Treatment outcomes vary between and within IAPT services, with between 24-71% of patients recovering after treatment, a large proportion improve without fully recovering, but a sizeable number do not improve at all or deteriorate while receiving treatment. This project aims to develop an algorithm that can predict prognosis for patients referred to IAPT services with depression. This is important because we are unable to determine what outcome a depressed patient referred to any given IAPT service will have, or account for the variability in outcomes between IAPT services. Predictions of outcome can inform decisions on whether or not a patient should start therapy, particularly for those most likely to not improve or deteriorate during treatment; help commissioners plan for the costs of treatment therefore saving the health service money, and compare between services while accounting for area-level differences and differences in the characteristics of referred patients; and allow services to focus resources on those likely to improve with treatment, potentially improving outcomes.

Amount: £228,328
Funder: The Wellcome Trust
Recipient: University College London

Transforming brain recordings with next-generation probes 30 Nov 2016

Thanks to the Wellcome Trust and other leading international institutions, we have developed and proved the viability of a new generation of recording probes that will transform electrophysiology. These "Neuropixels" probes transcend past approaches, recording hundreds to thousands of neurons simultaneously. Several key steps are now necessary to maximize the impact of this new technology, enabling its widespread use in the neuroscience community. We must develop radically new recording equipment and software, provide training, and build a collaborative community of users (Aim 1). To allow this community to fully exploit the potential of this technology, we must extend it to a larger range of applications: multi-shank probes, wireless recording for freely moving animals, and optrodes for use with optogenetics (Aim 2). Meanwhile, we will obtain ground-truth data to calibrate error rates, and begin the development of a tool to automatically identify brain regions based on electrophysiological characteristics (Aim 3). This project integrates software and hardware engineering, fabrication efforts, neurophysiology tests, and behavioral and anatomical techniques. It thus requires a collaboration between laboratories with different skill sets, and a unique nanoelectronics research partner, IMEC. The results of this collaboration will transform the field of neuroscience.

Amount: £1,674,199
Funder: The Wellcome Trust
Recipient: University College London

Resolving the functions of uncharacterised signalling proteins using zebrafish 19 Apr 2016

Signalling pathways orchestrate almost all aspects of development. The Schier lab has recently used ribosome profiling to identify numerous previously uncharacterised proteins that are expressed during early embryogenesis in zebrafish and might function as signalling molecules. One of the novel signalling proteins, previously annotated as a non-coding RNA, is Toddler (also called Apela or Elabela). Toddler signals via the APJ/Apelin receptor and promotes cell movement during gastrulation. The cellular and molecular roles of Toddler signalling are not known. My first aim as a Sir Henry Wellcome postdoctoral fellow will be to identify proteins that are regulated by Toddler signalling and reveal the cellular mechanisms that mediate the motogenic function of Toddler. My second aim is to employ a similar ribosome profiling approach to discover uncharacterised signalling molecules involved in the development of the nervous system. I will use genome engineering and take advantage of the complementary experience and expertise of the Schier and Wilson labs in behavioural and neuroanatomical studies to identify and analyse these signals. Their cellular and molecular functions will then be investigated. This project has the potential to discover signals with essential roles in neuronal migration, specification of neuronal identity and diversity, circuit formation and function.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University College London

Improving the long-term impact of child soldiering 31 Jan 2016

Little is known about the longitudinal effects of child soldiering onto the lives of these participants in wars, particularly in the children’s transition to adulthood. A culturally-grounded understanding of the multiple levels in which this experience shapes their subsequent lives in highly politicised communities is needed. My aim is to conduct a pilot assessing the feasibility of a future study on the long-term effects of early age involvement in political violence in the context of Nepal. This pilot will lay the foundation for a future application of funding for a larger research project. Knowledge of these effects will inform policy-makers and the rehabilitation services’ ability to support this population into adulthood. The funding will enable the facilitating of: i) A pilot in Nepal where I will reengage with my former PhD cohort of informants; ii) Workshops in Nepal and the UK to discuss the results of the pilots with scholars, informants, and stakeholders; iii) Time to prepare an academic paper. The key outputs will be: i) an assessment of the feasibility of the study; ii) the development of a network of collaborators; iii) an academic paper drafted for an academic journal. Key words: child soldiers, ethnopsychology, longitudinal research, war.

Amount: £10,000
Funder: The Wellcome Trust
Recipient: University College London

A computer assisted system to reduce auditory hallucinations unresponsive to antipsychotic medication 30 Sep 2016

About 25% of people with schizophrenia continue to suffer with persecutory auditory hallucinations despite drug treatment. Their capacity to work and make relationships is grossly impaired, often for the rest of their life. Professor Julian Leff from University College London and colleagues at Speech, Hearing and Phonetics, UCL have developed and evaluated a novel therapy based on computer technology which enables each patient to create an avatar of the entity (human or non-human) that they believe is talking to them. The therapist promotes a dialogue between the patient and the avatar in which the avatar progressively comes under the patient's control. This translation award aims to refine the system, streamline the technology to make it more user-friendly and evaluate the system by a randomised controlled trial conducted by an independent team of researchers at the Institute of Psychiatry, King's College London.

Amount: £34,060
Funder: The Wellcome Trust
Recipient: University College London

Development of a novel bioartificial liver device for the treatment of patients with liver failure 30 Sep 2016

In the UK, over 16,000 patients a year die of liver failure. Their livers have the capacity to repair and regenerate, but do not have time to do so. A device temporarily replacing liver function would save lives and reduce the necessity for liver transplantation worldwide. Dr Clare Selden and her team at UCL have developed a prototype 'bio-artificial liver' (BAL) to address this unmet need. Its key element comprises functioning liver cells in an external bioreactor. Plasma from a patient with liver failure will be passed through the bioreactor, contacting the alginate encapsulated liver cells, so that the cells replace those functions that the sick liver cannot perform. The machine will buy time for a patient's liver to improve or, if damage to the liver is irreversible, may buy time until liver transplantation can be arranged. The technology combines alginate encapsulation of a human liver cell line and subsequent culture of the encapsulated cells in a fluidised bed bioreactor - providing a convenient, manipulatable biomass in a form which maximises mass transfer between cells and perfusing plasma. The team have Translation Award funding to complete the design, specification, performance characterisation and manufacture of this fully biocompatible BAL.

Amount: £66,434
Funder: The Wellcome Trust
Recipient: University College London

Investigating the neural odometer function of entorhinal grid cells in rats navigating a multi-planar environment. 01 Apr 2016

It has been proposed that the grid cell system in the medial entorhinal cortex acts as a ‘neural odometer’, encoding both distance travelled and an animal's position in space. These features may be necessary for spatial computations such as path integration, but the relationship of grid cell firing patterns to behaviour remains speculative. In not-yet-published work, it has been shown that for a rat climbing a wall with its body plane aligned vertically the grid fields are expanded, as if the cells underestimate distance travelled. If grid cells support spatial computations then rats should also underestimate distances in this plane. To test this hypothesis rats will learn a distance match-to-sample task leading to triangle completion while both sample and choice phases are in the same plane (both horizontal or both vertical). In probe trials, the sample will be horizontal but the choice vertical. Distance underestimation in the probe trials (walking too far on the vertical wall to achieve a match to the horizontal sample) will link grid cells to behaviour, while the basic distance-matching task will serve as a springboard for neurobiological studies investigating the role of grid cells in odometry generally.

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

Epilepsy inducing mutation of the GABA-A receptor alpha 1 subunit 01 Apr 2016

We will investigate how a newly discovered mutation to the GABA-A receptor alpha 1 subunit gene (GABRA1) is causing epilepsy in a young child. A single mutation has been identified, which resides in the receptor's first transmembrane domain. This is near the previously identifed neurosteroid binding site from which endogenous neurosteroids can positively modulate GABA-A receptor activity. To investigate the implications of this mutation we have formulated the following aims that will be addressed using heterologous expression of GABA-A receptors in a cell line: 1. To establish the effect of the mutation on GABA concentration response curves and current voltage relationships for typical synaptic and extrasynaptic-type GABA receptors. 2. To determine if known allosteric modulators of GABA-A receptors are affected by the alpha1 subunit mutation. 3. To deduce if the expression levels and receptor mobility at the cell surface are affected by the alpha 1 subunit mutation. To achieve these goals, we will use a combination of patch clamp electrophysiology and single particle imaging techniques. This should establish whether the mutation is causing a gain- or loss-of function, or affects receptor trafficking.

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