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Funders:
Paul Hamlyn Foundation
The Wellcome Trust
Scottish Council For Voluntary Organisations
Community Foundation for Surrey
The Henry Smith Charity
Award Year:
2018

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Results

Body Knowledge in Post-War Humanitarian Campaigns 17 May 2018

<p>The project will look at the different ways in which&nbsp;the body has been used to mobilise public support for&nbsp;humanitarian campaigns in the post-war period. Drawing on the recently catalogued Oxfam collections at the Bodleian Library and the records of the British Leprosy Relief Association (LEPRA) at the Wellcome Library, the project will show how donor and recipient bodies have functioned as sites of learning and feeling. It focuses on two types of activity: the use of medical discourses to describe the suffering bodies of recipients of aid; and donors&rsquo; use of self-denial and physical hardship to increase bodily empathy with recipients.</p> <p>By uncovering the different kinds of body knowledge that were developed in this period, the goal is introduce a medical humanities perspective to the history of post-war humanitarian sentiment. In the short term, I will write a journal article on my case studies in the post-war period. In the long term I will use the research as a foundation from which to develop an interdisciplinary collaborative project on embodied empathy, and as the starting point for a monograph on changing attitudes towards body knowledge in humanitarian work in the nineteenth and twentieth centuries.</p>

Amount: £11,833
Funder: The Wellcome Trust
Recipient: University of Liverpool

Transforming Research Management in Africa 30 Sep 2018

<p>This application seeks funding for salary support for the Research Systems Manager (RSM) at The African Academy of Sciences for two years and a series of activities for one year that will inform a larger Programme of Work on &ldquo;Transforming Research Management in Africa&rdquo;. Further funding will be sought after this period. The initial activities are;</p> <ol> <li><strong>UK Visit: </strong>Allen Mukhwana, RSM, visited the UK 1 &ndash; 17 March. She visited the Wellcome for orientation and met with potential co-funders and partners.&nbsp;</li> </ol> <ol start="2"> <li><strong>Stakeholder Consultative meeting: </strong>A meeting was held in Nairobi on 8<sup>th</sup> and 9<sup>th</sup> February to discuss the Programme.&nbsp; &nbsp;&nbsp;</li> <li><strong>Baseline Survey:</strong>&nbsp;to assess capacities across African institutions to inform interventions.&nbsp;</li> <li><strong>Engagement with Deputy Vice Chancellors in Addis Ababa: </strong>RSM attended this meeting.&nbsp;&nbsp;</li> <li><strong>H3Africa Inception meeting, Entebbe&nbsp;</strong>20 - 23 March<strong>: </strong>RSM<strong>&nbsp;</strong>will attend to&nbsp;promote&nbsp;the Programme.&nbsp;</li> <li><strong>INORMS:</strong> 25 research managers will&nbsp;participate in the International Network of Research Management Societies meeting in Edinburgh 3 &ndash; 8 June 2018. &nbsp; &nbsp;</li> <li><strong>Site support visits:</strong>&nbsp;to work with the managers to improve their research environment and management.</li> <li><strong>DELTAS Africa Annual General Meeting:</strong>&nbsp;promote Programme 6-11 July.&nbsp;&nbsp;</li> <li><strong>Programme Development &amp; Networking opportunities: </strong>RSM will attend the regional associations&nbsp;(RIMAs) meetings/conferences to promote the Programme.</li> </ol>

Amount: £209,603
Funder: The Wellcome Trust
Recipient: African Academy of Sciences

Creating a new legacy collection for the British Library For Development Studies 21 Nov 2018

<p>Located at the University of Sussex and jointly managed with the Institute of Development Studies (IDS), the British Library for Development Studies (BLDS) historic collection tracks the unfolding story of international development and health systems in the Global South over the last half century.&nbsp; The collection is one of the most comprehensive in its coverage of government and official sources, particularly published in sub-Saharan Africa and South Asia between the mid-1960s and mid-1990s.</p> <p>Gradual reductions in funding, combined with a shift towards historical research in development studies and global health, have created a perfect opportunity to restore this archive.&nbsp; Much is uncatalogued, a local classification scheme makes it difficult to find material, and the collection&rsquo;s research value is unpublicised.<br> <br> The proposed project will enable the collection to be reshaped and positioned as an invaluable research resource for a new generation of scholars by:<br> <br> Honing the existing collection to focus on rare and unique holdings;<br> Increasing accessibility by cataloguing unlisted material, developing a standardised online search tool and undertaking preservation of fragile items;<br> Generating interest and awareness of an eventual new BLDS Legacy Collection through a launch event, public seminars, social media and a special historical issue of the IDS Bulletin.</p>

Amount: £405,485
Funder: The Wellcome Trust
Recipient: University of Sussex

Unboxing the boxer: cataloguing papers relating to sport at De Montfort University Special Collecitons 21 Nov 2018

<p>This project will facilitate access to a number of significant collections relating to the history of sport&nbsp;in the United Kingdom held in De Montfort University Special Collections, which are not being used to their full potential because they are difficult to retrieve and access. These comprise papers of the Amateur Boxing Association, Sir Norman Chester, Ski Club of Great Britain and the&nbsp;Special Olympics. Together these collections reflect research themes including widening participation in physical activity for health and wellbeing, elitism, exclusion and the place of&nbsp;minority groups in sport, and addressing societal &lsquo;illness&rsquo; such as violence and aggression. The item-level cataloguing of these collections will provide invaluable teaching and learning resources for the university and open up the archives for investigation by the international research community.</p> <p>The objectives of the project are to:&nbsp;</p> <ul> <li>create an item-level ISAD(G) compliant catalogue of each collection, hosted online</li> <li>rehouse the collections in appropriate archival packaging</li> <li>identify at-risk items and seek conservation treatment if necessary&nbsp;</li> <li>conduct migration to different formats where necessary</li> <li>publicise the project to internal and external research audiences and the general public</li> <li>assist the Heritage Centre Coordinator with a sports heritage exhibition</li> </ul>

Amount: £102,772
Funder: The Wellcome Trust
Recipient: De Montfort University

Making Wildfilm History Archive 21 Nov 2018

<p>The Wildfilm History Project will catalogue, conserve and make available a rich, diverse and important collection of wildlife filmmaking materials which document the changing cultural context of wildlife film making and how it has shaped our historical, social and cultural understanding of the natural world,&nbsp;as well as the growing appreciation of conservation issues and the broad public understanding of science. Key goals of the project will be to:</p> <p>&nbsp;</p> <ul> <li> <p>Create a detailed catalogue of the wide range of materials contained within the archive, including some of the most important wildlife films during the last hundred years</p> </li> <li> <p>Digitise and provide access to a prioritised selection of the archive and make this publicly available (where rights allow) through the University&rsquo;s Digital Archival Management system</p> </li> <li> <p>Ensure the physical and digital archive is preserved to enable the long-term access for researchers and the wider public.</p> </li> </ul>

Amount: £149,936
Funder: The Wellcome Trust
Recipient: University of Bristol

Transforming Lives: Cataloguing the history of social welfare and health at Barnardo's (1867 - 1980) 21 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">Since 1867, Barnardo&rsquo;s archival collections have continuously captured the&nbsp;role the charity has played in supporting hundreds of thousands of children and families through vital services, projects, research and campaigns. Essentially, they illustrate the large influence the charity has had on the progress of social welfare policy and practice for children in the UK, during the last two centuries.</p> <p style="margin-left: 0cm; margin-right: 0cm">Thus far, the Archive Service has only had the facilities and resources to support a small number of key research projects, therefore, the aim of the project is to raise awareness of the value of these collections, increase levels of access and more widely engage with health-related humanities and social science research audiences.</p> <p>To achieve these aims, a Project Archivist and Archive Assistant will be appointed to increase access through the arrangement, description and cataloguing of two of Barnardo&rsquo;s collections; the Child Care Records Collection&nbsp;and the Corporate Collection. They will also be tasked with developing a plan to increase engagement and raise awareness of the collections within the academic research community.</p> <p>The final&nbsp;objective of the project will be to ensure the&nbsp;successful conservation of 126 of Barnardo's most frequently accessed bound volumes.</p>

Amount: £170,696
Funder: The Wellcome Trust
Recipient: Barnardos

Worcestershire's Health Record 21 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">The project proposes to increase the variety of sources available for the study of medicine, health and welfare in Worcestershire by cataloguing and conserving a range of collections from our backlog and retroconverting old paper catalogues relating to hospitals and health professionals and organisations pre and post the formation of the NHS.&nbsp; This will build on our previous project cataloguing the mental health records of Barnsley Hall and Powick Hospitals.</p> <p style="margin-left: 0cm; margin-right: 0cm">The project objectives are:</p> <p style="margin-left: 0cm; margin-right: 0cm">To create catalogues of our unlisted health related collections to international standards for use by &nbsp;medical professionals and researchers and the general public, subject to any limitations imposed by the confidential or sensitive nature of the material. The catalogues will be available at http://www.worcestershire.gov/CalmView/</p> <p style="margin-left: 0cm; margin-right: 0cm">To retroconvert our pre CALM paper catalogues relating to health/hospital records so that they can be accessed online.&nbsp;</p> <p style="margin-left: 0cm; margin-right: 0cm">To clean, preserve, repackage into appropriately sized boxes and folders and repair fragile items in the collections</p> <p style="margin-left: 0cm; margin-right: 0cm">To promote the project as it progresses and raise awareness of our medical and health records holdings by means of social media, &nbsp;articles in relevant newsletters, an exhibition, presentations at workshops/day schools and a health walk</p> <p style="margin-left: 0cm; margin-right: 0cm">To produce an online guide outlining our main health archive collections</p>

Mining the seams: Opening Derbyshire's and Warwickshire's coal collections 21 Nov 2018

<p>Derbyshire and Warwickshire Record Offices will work together to catalogue National Coal Board, Midland Colliery Owners Mutual Indemnity Company&nbsp;and Warwickshire Miners Association collections making them accessible&nbsp;to reasearchers for the first time.&nbsp;&lsquo;Mining the Seams&rsquo; expands on Derbyshire's previous National Union of Mineworkers (NUM) project to open up the complete coal archives for two Midlands counties.</p> <p>This project will&nbsp;share new cataloguing approaches and work with the academic community to&nbsp;expand awareness of the impact of industrial accidents on safety legislation, specialisms within the NHS, local communities and on Britain's industrial history.&nbsp;&nbsp;Working collaboratively with an academic advisory panel, students and local volunteers, we will create resources to stimulate new research into the coal industry and:</p> <ul> <li>Jointly catalogue, repackage, problem solve&nbsp;and improve access to 257 metres of coal-mining collections;</li> <li>Develop better ways of working with universities and other research organisations</li> <li>Conserve more than 1000 items, including photographs, plans, and volumes;</li> <li>Create an anonymised dataset of Workmen's Compensation data from Warwickshire and Derbyshire to complementing Derbyshire's NUM dataset, enabling online&nbsp;statistical and comparative analysis across the two counties;</li> <li>Digitise 5000 pages, trialling jpeg2000&nbsp;to provide new access points;</li> <li>Develop two study days at the Universities of Warwick and Derby.</li> </ul>

Amount: £242,721
Funder: The Wellcome Trust
Recipient: Derbyshire County Council

Dorset's Asylum - the Herrison Hospital Archive 21 Nov 2018

<p>This project consists of three principal strands:</p> <p>1) Cataloguing</p> <p>A fundamentally important part of this project is to fully understand and document the contents of the Herrison Hospital archive.&nbsp; Without a proper and consistent catalogue, the archive will remain largely anonymous, out of reach to all but the most determined and patient of researchers.&nbsp; A key output of the project will therefore be a full, structured, electronic catalogue which will promote quick and efficient identification and retrieval of relevant parts of the archive.</p> <p>2) Conservation and preservation</p> <p>An important counterpart to the catalogue description of the archive is the work that will be undertaken to conserve and promote&nbsp;its long-term preservation.&nbsp; There is a significant quantity of the archive which upon which remedial conservation will need to be performed.&nbsp; This sits alongside the packaging and boxing of the archive in suitable materials to assist with its preservation when in the repositories.</p> <p>3) Academic investigation and analysis</p> <p>Working with John Clews, a doctoral candidate, it will be possible to undertake academic analysis of the archive whilst it is being catalogued.&nbsp; John will assist in this regard whilst hosting public engagement events and promoting the archive.</p>

Amount: £56,650
Funder: The Wellcome Trust
Recipient: Dorset History Centre

iAWARE: Work-Based Online Psychoeducation for the Enhancement of Employees’ Mental Health Literacy and Workplace Wellbeing 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">This project encompasses development of online work-based mental health training using co-production with employees at participating organisations, and testing feasibility of incorporating this tool into organisational strategies for improving employees&rsquo; mental wellbeing.</p> <p style="margin-left: 0cm; margin-right: 0cm">iAWARE would be unique in that it would be designed within a complex intervention framework with the explicit objective of forming one component within a systemic approach to workplace wellbeing. This would be achieved by a) allowing for material to be tailored to particular organisation contexts and b) including a reporting function whereby data generated non-reactively through use of the programme is used to inform employers for development at the organisational level.</p> <p style="margin-left: 0cm; margin-right: 0cm">Future will involve robust pilot testing and evaluation, subject to progression criteria, namely indicative positive changes in mental health literacy from baseline for participants in the first phase study, and proven feasibility of integration into diverse complex organisational settings.</p>

Amount: £85,919
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Towards in vivo genome editing of post-mitotic mammalian photoreceptors for treatment of Inherited Retinal Dystrophies 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">Retinitis Pigmentosa (RP) causes untreatable visual loss. Gene augmentation trials for genetic eye disease have disappointed, partly due to difficulties in optimising correct, persistent exogenous gene expression. The possibility of precise, efficient gene correction using genome editing technology for highly genetically heterogenous diseases like RP would overcome these dosage issues.</p> <p style="margin-left: 0cm; margin-right: 0cm">&nbsp;</p> <p style="margin-left: 0cm; margin-right: 0cm">To determine the feasibility of genome editing, we have developed powerful fluorescent reporter mouse models, allowing sensitive readouts of editing events in time and space. Using these, we demonstrated post-natal murine photoreceptors are amenable to genome editing in retinal explants. However, several obstacles exist to making editing a reality in the disease setting. This project aims to:</p> <p style="margin-left: 0cm; margin-right: 0cm">&nbsp;</p> <ol> <li>optimise targeted editing machinery delivery to photoreceptors <em>in vivo</em>;</li> <li>improve photoreceptor repair efficiency;</li> <li>explore novel, homology-independent strategies for photoreceptor gene correction;</li> <li>assess potential for editing technology to rescue vision.</li> </ol> <p style="margin-left: 0cm; margin-right: 0cm">&nbsp;</p> <p style="margin-left: 0cm; margin-right: 0cm">To expedite solutions, we propose using our reporter models to develop <em>in vivo</em> photoreceptor editing. We have prepared retinotrophic AAV serotypes containing machinery necessary to edit our models. Following optimisation in reporter models, we will assess repair of disease-causing mutations in our humanised mouse RP models.</p> <p style="margin-left: 0cm; margin-right: 0cm">&nbsp;</p> <p style="margin-left: 0cm; margin-right: 0cm">These experiments will provide vital pilot data towards securing industrial partnerships to translate this technology into clinic.</p>

Amount: £98,979
Funder: The Wellcome Trust
Recipient: University of Edinburgh

Quantitative evaluation of gene dosage effects in the Ras/ERK and PI3K/mTOR pathways on metastatic transformation of oesophageal cancer 02 Nov 2018

<p>Distant metastases account for ~90% of cancer-related deaths, but our understanding of the determinants of this process is limited. I propose to elucidate early genomic mechanisms that enable cells to acquire a metastatic phenotype, with focus on allelic imbalance resulting from copy number changes and the underlying genomic instability. I have previously characterized the implications of genomic amplifications of receptor tyrosine kinases and downstream pathways (MAPK/ERK/PI3K) in the progression of oesophageal adenocarcinoma, a cancer with frequent metastases and prevalent genomic instability. Recent studies have highlighted similar gene dosage effects in KRAS promoting metastasis in pancreatic cancer, and a more general role for genomic instability in accelerating metastatic spread.</p> <p>This study proposes to explore the involvement of such alterations in local invasion in oesophageal adenocarcinoma using whole-genome and RNA sequencing data from primary tumours of this type. I aim to: (1) characterize gene dosage effects and co-dependencies at genomic/transcriptional level in the Ras/MAPK and PI3K/AKT pathways; (2) understand the mutational processes generating such alterations; (3) employ machine learning to identify features in 1) and 2) that are predictive of cellular invasion in this cancer. This integrated framework will highlight pathway vulnerabilities during metastatic onset that may be targetable in the clinic.</p>

Amount: £99,983
Funder: The Wellcome Trust
Recipient: University College London

Profiling the effect of the metabolite formaldehyde during gemcitabine chemotherapy 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm"><strong>Scientific Problem</strong>: Gemcitabine, a widely used anti-cancer drug, is susceptible to enzymatic inactivation in human cancer cells. This inactivation is catalysed by cytidine deaminase, which is often over-expressed in cancer. Novel strategies to reduce gemcitabine inactivation are therefore essential for avoiding chemo-resistance to gemcitabine and related chemotherapy drugs.</p> <p style="margin-left: 0cm; margin-right: 0cm"><strong>Key Goals</strong>: I have shown that gemcitabine reacts reversibly with the human metabolite formaldehyde to form an adduct resistant to deaminase catalysis. This exciting result suggests intracellular formaldehyde can regulate gemcitabine&rsquo;s anti-cancer activity. The aims of this project are to (1) determine whether increasing formaldehyde concentrations increases gemcitabine&rsquo;s cytotoxicity, (2) correlate low cellular formaldehyde concentrations with gemcitabine resistance, and (3) assess whether formaldehyde reacts with and regulates the stability of gemcitabine in cells. &nbsp;</p> <p><strong>Importance/Impact</strong>: The project will be the first to assess how formaldehyde regulates the activity of gemcitabine, and by extension, cytidine nucleotides in cells. The work will therefore stimulate development of combination therapies (e.g. co-treatment of gemcitabine and formaldehyde-releasing small molecules), and development of prodrugs incorporating dual formaldehyde and gemcitabine release. More generally, the work will be the first to validate formaldehyde modulation as a therapeutic strategy. The work will also provide crucial MS methods for studies on formaldehyde biology.</p>

Amount: £99,696
Funder: The Wellcome Trust
Recipient: University of Leicester

Understanding the role of the respiratory tract microbiota in immunity to bacterial infection in COPD 02 Nov 2018

<p style="margin-left: 0in; margin-right: 0in">Understanding how the recently identified airway microbiota interacts with the unique immune system of the lung to protect against infection in health and how these interactions are disturbed in COPD is a crucial question both clinically and biologically. Since cause/effect cannot be inferred from human studies, I will utilise microbiota manipulation in novel murine models to understand the function of the airway microbiota in shaping lung-specific immunity and defining infection susceptibility. I hypothesise that commensals perturbed within the COPD airway microbiota can influence infection susceptibility through modulation of the anti-microbial peptide cathelicidin. Aim 1 will build on my previously developed novel murine model of selective respiratory tract microbiota depletion to understand how the airway microbiota affects immunity to bacterial infection. Aim 2 will utilise gain/loss of function experiments to interrogate the role of cathelicidin in microbiota-induced protection against infection. Aim 3 will examine whether commensals associated with disease/health that are perturbed in COPD patients who frequently exacerbate can modulate lung-specific immunity and infection susceptibility. Key goals will be:(1) Development of robust murine models of microbiota manipulation. (2) Generation of preliminary data to provide feasibility for Fellowship applications. (3) Development of new skills in bacteriology/molecular microbiology to facilitate development of independence.</p>

Amount: £50,000
Funder: The Wellcome Trust
Recipient: Imperial College London

Boosting sleep to promote myelination 02 Nov 2018

<p style="margin-left: 0in; margin-right: 0in">Myelin, the fatty substance surrounding nerve fibers, is essential for proper brain functioning. Loss of myelin integrity characterizes several debilitating diseases, such as multiple sclerosis. Thus, understanding the factors that can modulate myelin formation and maintenance is crucial for these diseases.</p> <p style="margin-left: 0in; margin-right: 0in">My recent work has shown that:</p> <ul> <li>Sleep favors the expression of genes implicated in myelin formation and myelin lipid turnover.</li> <li>Oligodendrocyte precursors that form the major source of newly formed myelinating-oligodendrocytes in the brain proliferate preferentially during sleep.</li> <li>By contrast, sleep restriction leads to myelin thinning, suggesting sleep is an essential requirement for maintaining myelin integrity.</li> </ul> <p style="margin-left: 0in; margin-right: 0in">These results raise the intriguing question: can we promote myelination by enhancing sleep?</p> <p style="margin-left: 0in; margin-right: 0in">Here, I will use closed-loop acoustic stimulation in sleeping mice to enhance NREM and REM sleep. Increasing evidence has shown that this method can reliably boost cardinal neurophysiological features of NREM and REM sleep in both rodents and humans. This approach will allow me to verify whether sleep enhancement promotes myelination in the mouse forebrain.</p> <p style="margin-left: 0in; margin-right: 0in">This research will advance our knowledge about the factors that regulate myelination. Furthermore, it will provide insight into new possible ways of intervention in Multiple Sclerosis and related disorders based on sleep enhancement.</p> <p style="margin-left: 0in; margin-right: 0in">&nbsp;</p>

Amount: £99,201
Funder: The Wellcome Trust
Recipient: University of Bristol

The genetics and epigenetics underpinning a broad spectrum of human fungal pathogens 02 Nov 2018

<p>Fungal pathogens are a global threat to human health. Few antifungal drugs are effective, and even these are becoming less useful as fungi increasingly develop resistance. New treatments and mitigation efforts are hampered by the lack of basic science on the genetic basis of virulence in these pathogens. I will address this, by describing how pathogenic fungi regulate gene expression by genetic and epigenetic means in cell culture <em>vs. ex vivo</em> (macrophages). I will further<br> characterize and verify regulatory networks, changes to nucleosome positions and histone modifications in response to macrophages. Foci may include the cell membrane component ergosterol, which is an important antifungal drug target, as well as capsule genes that are essential virulence factors in some pathogens. By comparing across multiple pathogen systems, I will identify the extent genomic instability provides a mechanism for adaptation, how gene expression correlates with the host environment and what role chromatin state plays in virulence. Understanding the molecular mechanisms that drive the evolution of these phenotypic determinants will enable the development of new remedial measures.</p>

Amount: £97,523
Funder: The Wellcome Trust
Recipient: University of Exeter

Non-canonical G protein signalling: toward new therapeutic avenues 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">G protein-coupled receptors (GPCRs) represent the largest family of cell surface proteins. Agonist binding to GPCRs activates G proteins regulating many cellular effectors. Classically, G protein activation occurs at the plasma membrane and is rapidly terminated by&nbsp;&beta;-arrestin recruitment to the activated GPCRs, promoting G protein uncoupling from receptor, GPCR internalisation and signalling arrest.</p> <p style="margin-left: 0cm; margin-right: 0cm">However, recent studies revealed that upon internalisation, some GPCRs continue to activate G proteins from internal compartments leading to sustained production of second messengers far from the plasma membrane. This different spatiotemporal signalling profile allows distinct cellular functions from the ones occurring at the plasma membrane that can be exploited in the near future to design new pharmacological approaches. My collaborators and I recently observed that for some GPCRs such as the vasopressin type 2 receptor, formation of a GPCR-G protein-&beta;-arrestin complex (baptised megaplex) in internal compartments is required for non-canonical Gs protein signalling. The initial research programme I propose aims to tackle the following important questions underlying this novel signalling mode:</p> <p style="margin-left: 0cm; margin-right: 0cm"><strong>1. Is G protein selectivity different at intracellular compartments vs at plasma membrane?</strong></p> <p style="margin-left: 0cm; margin-right: 0cm"><strong>2. Is megaplex formation restricted to Gs isoform?</strong></p> <p style="margin-left: 0cm; margin-right: 0cm"><strong>3. What is the specific role of&nbsp;&beta;-arrestin within the megaplex?</strong></p>

Amount: £100,000
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Developing models to investigate how malignant B cells interact with cognate antigen in physiological conditions 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">Accumulating evidence suggests that antigen-induced B cell receptor (BCR) signalling plays a role in the pathogenesis of Chronic Lymphocytic Leukaemia (CLL). However, how the interaction with specific antigens drives CLL expansion is unclear. With this award, I aim to develop a set of tools to investigate how CLL cells interact with antigen presented in conditions that resemble the tumour micro-environment and, how the interaction with antigen drives expansion of malignant B cells <em>in vivo</em>.</p> <p style="margin-left: 0cm; margin-right: 0cm">To examine how CLL cells interact with antigen at a single cell and single molecule level, I will develop a high-content large-scale imaging approach. To mimic how B cells engage antigen <em>in vivo</em>, I will load antigen on flexible membrane substrates that closely resemble the physical characteristics of follicular dendritic cells (FDCs), from where B cells normally acquire antigen. I will then analyse how efficient CLL cells are at immune synapse formation, BCR signalling and antigen internalisation. To investigate how the interaction with antigen drives CLL expansion&nbsp;<em>in vivo</em>, I will target antigen to the surface of FDCs in mouse lymph nodes and then transfer antigen-specific CLL&nbsp;cells isolated from a CLL mouse model. Subsequently, I will analyse&nbsp;activation and proliferation of transferred CLL cells.</p>

Amount: £98,332
Funder: The Wellcome Trust
Recipient: King's College London

Mapping the consequences of peripheral nerve transection and repair on brain organisation and hand function. 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">Damage to the peripheral nerves of the hand dramatically disrupts feeling and movement, and precipitates a variety of reorganisational changes in the brain. Preliminary evidence from our work with hand transplant and replant recipients suggests that such changes are maladaptive and limit recovery. Specifically, we find that passive cutaneous stimulation of the uninjured hand results in significant positive functional MRI (fMRI) activity in ipsilateral primary sensory cortex (S1), and moreover, the strength of this activity negatively correlates with sensory performance. Positive ipsilateral S1 activity during hand stimulation is not observed in healthy controls, and represents a marker of trauma-related interhemispheric reorganization.</p> <p style="margin-left: 0cm; margin-right: 0cm">Building from these initial data, which are limited by few patient cases, the proposed research will investigate the clinical significance of nerve-trauma-related brain changes in the more numerous conditions of median/ulnar and digital nerve injury and repair. Using our established fMRI and behavioural methods, we expect to identify brain changes in patients that predict poor sensory performance of the injured hand. This research will significantly advance our understanding of the functional consequences of brain changes following nerve damage to the hand, and set the stage for the development of new rehabilitation therapies designed to help reverse these changes.</p>

Amount: £94,063
Funder: The Wellcome Trust
Recipient: Bangor University

Assessing the operational usage of drone imagery for malaria mosquito breeding site mapping in Malawi (Maladrone) 02 Nov 2018

<p style="margin-left: 0cm; margin-right: 0cm">In Malawi, despite significant advances in malaria control, the progress being made using approaches such as the distribution of long-lasting impregnated nets (LLINs) is showing signs of slowing down. Supplementary approaches that target high transmission areas are therefore needed such as modifying or manipulating potential mosquito breeding sites so that the mosquitoes are no longer able to develop. This is&nbsp;referred to as larval source management (LSM). This proposal aims to assess whether drone imagery can feasibly be used by the national malaria control programme (NMCP) in Malawi to target activities such as LSM. Field studies will be conducted within the UNICEF humanitarian drone testing corridor in Kasungu district, Central Malawi to determine if the mosquito breeding sites can be pragmatically identified using drones, and to establish a framework by which the NMCP could adopt this technology. The capabilities of multiple drones and a range of open source and commercial image processing approaches will be compared to establish a balance between habitat identification accuracy and usability. Further data including larval samples, adult mosquito catches and clinical malaria case data will be collected to explore whether breeding site location can be used to identify malaria transmission hotspots within the area.</p>

Amount: £97,649
Funder: The Wellcome Trust
Recipient: Lancaster University