- Total grants
- Total funders
- Total recipients
- Earliest award date
- 11 Jan 2016
- Latest award date
- 06 Dec 2016
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Cellular and network mechanisms of hippocampal -prefrontal coordination during memory consolidation 09 Nov 2016
Consolidation of newly acquired memories takes place during sleep and involves the interaction of hippocampus and prefrontal cortex. The cellular mechanisms and synaptic pathways underlying this process are not fully understood but it has been hypothesized that synchronous hippocampal ripples and prefrontal cortex spindles mediate it. The present project proposes a multimodal approach to investigate these mechanisms in rodents. The first goal will be to dissect the fine-scale dynamics of memory reactivation in hippocampus and cortex during sleep after learning of a spatial memory task. This aim will be achieved with simultaneous large-scale recordings in both structures and advanced analysis of population activity. The second goal will be to unveil which anatomical regions and synaptic pathways are mediating this inter-regional synchronization. Simultaneous electrophysiological and functional magnetic resonance recordings will be performed in sleeping rats before and after the task and wide-brain activity will be assessed at times of high hippocampal-prefrontal synchrony. The last goal will be to causally verify the participation in inter-areal coordination and memory consolidation of the key synaptic pathway(s) pointed out in the previous stage. To achieve this, closed-loop optogenetic silencing of specific cellular populations would be performed at times of hippocampal-prefrontal synchrony during sleep memory consolidation.
Neural Circuits for Selective Auditory Filtering 05 Apr 2016
To facilitate sensory processing in complex environments, the brain can selectively filter auditory input to enhance neural responses to relevant sounds and suppress responses to background distractors. Neural correlates of selective filtering have been observed in auditory cortex (AC), but the underlying neural circuitry has not yet been identified. A synthesis of existing results and our preliminary data suggests that selective auditory filtering arises through interactions between AC and two thalamic structures: the medial geniculate body (MGB), which sends direct excitatory input to AC and receives direct excitatory feedback from AC, and the thalamic reticular nucleus (TRN), which relays indirect inhibitory feedback from AC to MGB. In this proposal, we outline a plan to answer three key questions related to selective filtering: Q1: Are selective spectral and temporal filtering evident in the auditory thalamus? Q2: How do thalamocortical interactions contribute to spectral and temporal filtering? Q3: How does attention modulate spectral and temporal filtering? The proposed experiments will lead to significant advances in our knowledge of the general mechanisms that underlie active sensory processing in all mammals, while also helping build toward a detailed understanding of the neural circuitry that allows humans to understand speech in noisy environments.
Genome-wide association studies (GWAS) have greatly improved our understanding of human disease genetics, and are beginning to be applied to pathogens. Current pathogen GWAS have largely focused on the identification of variants behind bacteria and parasite drug resistance. A neglected application is identifying variants determining infectiousness for viruses such as HIV-1. HIV transmission is influenced in large part by an individual’s set point viral load (spVL), which itself is determined by variation in the viral genome. Given HIV’s short genome and large amount of common genetic diversity, spVL provides a tractable target in terms of potential pathogen GWAS with large global health implications. During this fellowship I will first adapt GWAS to HIV whole genome sequences by focusing on drug resistance, a phenotype where many variants are already well understood. Once the methods are perfected, I will analyse spVL in the PANGEA_HIV sample of 20,000 whole genome sequences. Identified variants will be combined with demographic data to understand how they influence transmission on a population level. They will also be tested for interactions with host genetic variants, to understand the biology of immune escape. This will allow for a better understanding of transmission risk.
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.
Climate change threatens to undermine the foundations of human wellbeing, and to reverse the last five decades of gains in global health. The 2015 Lancet Commission on Health and Climate Change concludes that the barriers to tackling climate change and improving public health are no longer economic or technological, but largely political. The report also concludes that "tackling climate change could be the greatest global health opportunity of the 21st century", with reduced greenhouse gas emissions yielding substantial health (and economic) gains. The Commission is an institutional collaboration between European and Chinese academic centres, led by University College London, Tsinghua University (Beijing), the University of Exeter, and Sweden’s Stockholm Resilience Centre and Umea University. It published its work on the 23rd of June, 2015 in The Lancet, with 11 launch events around the world. The authors of the Commission report recognise the need to carry their work forward- and to help deliver the required change. They propose a "Countdown to 2030: Global Health and Climate Action" as a mechanism for tracking progress on the implementation of policies designed to respond to climate change and protect public health. This idea draws upon the success of the Countdown to Child Survival, which galvanised evidence, interest and action to improve progress on child mortality over the past decade. The Countdown will exist as an independent, international, and multi-disciplinary coalition of organizations. The combined networks of The Lancet and the partner institutions will be utilized to ensure global reach to academics, policymakers, and the health community. It will produce an annual synthesis report on (i) the health impacts of climate change; (ii) progress in mitigation policies and the extent to which they protect and promote public health; (iii) progress with broader adaptation action to reduce population vulnerability, to build climate resilience, and to implement low carbon, sustainable health systems. The Countdown will continue its collaboration with The Lancet, who commit to publishing these Countdown Reports, as well as a number of related country- or issue-specific articles throughout each year.
Liver disease is the 5th commonest cause of death in the UK and the only one of the top 10 currently rising. Approximately 110,000 patients with symptoms of advanced cirrhosis, (commonly related to alcohol excess) e.g. jaundice, confusion and bleeding from the stomach, were admitted to UK hospitals in 2011-12. The most common cause of death in these patients is infection. These patients have a weakened immune system making them highly vulnerable to infection and no effective strategy exists to improve this. A research group headed by Dr Alastair O'Brien at University College London discovered that the cause of this vulnerability is an increase in blood levels of a lipid hormone called Prostaglandin E2 (PGE2) which reduces white blood cell function, the cells that fight infection. They have discovered that their immune systems can be boosted for at least 24 hours by infusing albumin into a vein which reduces PGE/s effects. This safe process is currently given when patients need extra fluid e.g. those with kidney damage. They propose this new exciting use for albumin to be given daily to improve cirrhosis patients' immune systems and therefore prevent infection. They hope that this will save lives and reduce health-care costs and propose to investigate this in a large scale clinical trial
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.
Pancreatic cancer is a biologically aggressive cancer, which is resistant to chemotherapy and radiotherapy and has a high rate of recurrence. Surgical resection remains the only treatment with potential for long-term survival and cure. However, many patients have metastatic disease at presentation and a third have locally advanced pancreatic cancer, leaving only 10% - 20% suitable for potentially curative resection. Even after resection, recurrence is common and adjuvant chemotherapy is used but thermal ablation, which is established for palliation of other cancers, is not recommended for unresectable pancreatic cancer because of risk of injury to the pancreatic duct or nearby major blood vessels. This project will develop a patient-specific planning, simulation and intra-operative navigation system for individualised ablation and palliation of inoperable pancreatic cancer. We will investigate a new technique – irreversible electroporation ablation (IRE) – which causes cell death through a different mechanism to thermal ablation that can minimise damage to the pancreatic duct and major blood vessels. We will develop a navigation system so that accurate IRE electrode placement can be carried out percutaneously or under laparoscopic guidance. The potential impact of the project will be to prolong and increase the quality of life for a patient population with limited treatment options.
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.
We have identified an entirely new mechanism by which retroviruses regulate the process of DNA synthesis. We have discovered that, contrary to textbooks, the process of HIV-1 DNA synthesis occurs inside intact capsids and that the nucleotide fuel for DNA synthesis is sucked through regulated electrostatic channels formed by the hexmaeric capsid lattice making up the viral core. We have also discovered that the channels can open and close through a molecular iris formed by the capsid beta hairpin sequences at the 6-fold access of symmetry. This work is in press in Nature. Preliminary data suggest that non-pandemic forms of HIV do not properly regulate their capsid pores and that this causes these viruses to be less able to evade intracellular innate sensing mechanisms. This may explain their failure to reach pandemic levels of human-to-human transmission. Our current work aims to understand the molecular details of how pandemic HIV-1 regulates DNA synthesis through cofactor recruitment and regulation of the capsid channels. We also aim to understand whether the non-pandemic viruses also do this and to understand what features they lack. We also aim to understand when the process of channel regulation evolved, ie in the parental chimpanzee viruses or in humans as HIV-1.
This project will study the dynamic trajectories of materials like stainless steel, silicone rubber and PVC that make up clinical and direct-to-consumer healthcare products. I will follow materials as they move from manufacturing to the marketplace and beyond, exploring their perceived risks and rewards, and examining how the choices of materials scientists and designers influence users’ experiences of health and wellbeing. The project’s innovative tripartite method will afford a uniquely holistic understanding of human experiences of materials, combining ethnography, design research and psychophysics to allow for a simultaneous focus on the physical, sensory, aesthetic and cultural affordances of materials. My key goals are to firmly establish this new interdisciplinary approach, thereby providing a bridge between the laboratory, design studio, care environment and society, with the potential to influence design practice, research directions in materials science and practices and experiences of healthcare. In bringing together materials producers, designers, clinicians and users this project encourages dialogue and enables translation between isolated disciplinary and professional communities. It therefore takes crucial first steps towards the identification and development of materials that accord with clinical and societal needs.
In-hospital resuscitation under the microscope: Analyzing inter-professional communication using video 10 Mar 2016
The aim of this proposal is to explore the possibilities and challenges of video-recording inter-professional teams working to resuscitate patients on hospital wards following a cardiac arrest. Video recordings provide an essential data source for an approach to communication research which is now commonly used in the social sciences yet currently not widely applied in health research. This approach draws on recent theoretical and methodological advances in discourse analysis, which allow for the development of a much more fine grained and inclusive set of categories for describing communication. With this approach, currently largely tacit, unverified understandings of what counts as ‘good’ communication, teamwork and leadership can be made explicit, tested empirically, and refined accordingly. The Seed Award will bring together a strong, multi-disciplinary research team to jointly develop a methodological, ethical and legal framework for the envisioned research. This will be achieved through a simulation-based pilot study and engagement with stakeholders. The main outcomes of the Award will be an application for a large research grant, an ethics application and a methodological paper.
My aim is to develop a theoretical model of language processing that explains inter-patient variability in outcome after stroke. My hypotheses are that the same language task (e.g. describing a picture) can be sustained by different sets of brain regions (and neuronal pathways) and that inter-subject variability in neuronal pathways for the same language task reflect an individual’s inherent potential and prior experience. My investigations will (1) use functional neuroimaging to characterize inter-subject variability in neuronal pathways in a range of language tasks; (2) cluster healthy individuals and stroke patients into different groups according to the neural systems used for the same task; and (3) compare the identified groups on a multitude of demographic, behavioural and structural imaging measures. The results will identify the factors that distinguish which neuronal pathways a subject typically uses and which neural pathways are available to support recovery. The work will provide: (i) greater understanding of the neuronal pathways sustaining recovery; (ii) improved accuracy and precision in our prognoses for whether and when patients with aphasia will recover after stroke, and (iii) a new patient stratification system that can be used to design effective, individualised therapeutic interventions.
Minoritized Youth, addresses fundamental equity issues in informal STEM learning (SL+ priority D, Equity, diversity and access to informal learning settings). The major goal of our Partnership is for practitioners and researchers, working with minoritized youth, to develop new understandings of how and under what conditions minoritized youth participate in Informal STEM Learning (ISL) over time and across settings, and how they may connect these experiences towards pathways into STEM. We will: 1) Develop new understandings of ISL pathways that are equitable and transformative for minoritized youth; 2) Co-develop high leverage practices and tools that support these equitable and transformative ISL pathways (and the agency youth need to path-make); and 3) Strengthen and increase professional capacity to broaden participation among youth from minoritized communities in STEM through ISL. Our work is grounded in longitudinal youth participatory ethnographies, surveys, and design-based implementation research methodologies. Our major goal responds to three challenges at the intersections of ISL research and practice in the US/UK: 1) lack of shared understanding of how minoritized youth perceive and experience ISL opportunities across the US/UK, and the practices and tools needed to support empowered movement through ISL; 2) limited shared understanding and evidence of core high-leverage practices that support minoritized youth in progressing within and across ISL, and 3) limited understanding of how ISL might be equitable and transformative for minoritized youth seeking to develop their own pathways into STEM. We focus on minoritized youth, ages 11-14, for whom there are wide and persistent gaps in representation in STEM, and for whom STEM careers and pursuits remain elusive. The project will be carried out by RPPs in 4 cities: London & Bristol, UK and Lansing, MI & Portland, OR, US, involving university researchers (Kings College, University College London, Michigan State University, Oregon State University) practitioners in science museums (@Bristol Science Centre, Brent Lodge Park Animal Centre, Impressions 5, OMSI) and community-based centers (STEMettes, Knowle West Media Centre, Boys & Girls Clubs of Lansing, and Girls, Inc.).
Molecular Control of Adhesion-Free Migration 09 Nov 2016
Many cells have the capacity of directed motion, which is essential for several physiological and pathological processes, including development, immune-response, and metastasis. During canonical, focal adhesion-based migration, actin dynamics are converted to traction force through integrin-based anchors to the substrate. However, integrins are dispensable for in vivo and 3D-confined migration of various cell types. Recently, an alternative migration mode was discovered, during which propulsion forces are generated through non-specific friction between the cell cortex and its substrate. However, nothing is known about the molecular mechanism underlying friction-driven migration. I will elucidate this process, first by performing a candidate-based screen and state-of-the-art microfabrication assays to identify the molecules responsible for generating friction. Next, I will create knock-out zebrafish lines to determine the in vivo relevance of friction-driven migration. Finally, I will study how cells transition between adhesive and adhesion-free migration, which is crucial e.g. during cancer progression. To identify the key processes underlying these transitions, I will perform live cell microscopy of friction-generating and adhesion molecules and integrate my findings into a mathematical model of cell migration. Ultimately, this project will shed light on a newly uncovered migration mode that is likely of fundamental importance for in vivo cell motility.
Wellcome Centre for Human Neuroimaging 30 Oct 2016
Our vision is to deliver clinically-transformative applications of neuroimaging that provide computationally-derived biomarkers for personalised prognosis and treatment planning. We investigate how the human brain functions in health and disease and how this knowledge can inform prognoses in patients with neurological and psychiatric disorders. By integrating cutting-edge neuroimaging technologies with neuronal and behavioural modelling, we seek to establish non-invasive quantitative measures of neuronal function that can be used to identify pathophysiology, deliver personalised prognoses, and develop or assess therapeutic interventions. Our strategy combines two key elements that are unique to our location, staff and facilities. First, we bring together internationally-renowned expertise in neuroimaging, biophysical modelling, cognitive, computational, mathematical and clinical neuroscience. Second, we create an environment that fosters interactions between those asking key neurobiological questions and those developing methods and theories that make these questions tractable. Our clinical focus reflects a long-standing commitment to developing neuroimaging methods that provide mechanistic explanations of how the human brain supports sensory, motor and cognitive functions in health, how these mechanisms are affected by disease, and how they respond to therapeutic interventions. We are in a unique position to conduct this work given our our location opposite the National Hospital for Neurology and Neurosurgery.
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