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Funders:
The Wellcome Trust
Recipients:
University College London
University of Oxford
Award Year:
2016

Results

Partnering for Equitable STEM Pathways for Youth from Minoritized Communities. 07 Nov 2016

<p>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.&nbsp; 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.&nbsp; The project will be carried out by RPPs in 4 cities: London &amp; Bristol, UK and Lansing, MI &amp; 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 &amp; Girls Clubs of Lansing, and Girls, Inc.).</p>

Amount: £749,245
Funder: The Wellcome Trust
Recipient: University College London

The Opie archive: exploring play in Britain from the 1950s to the 1980s 25 Nov 2016

<p>This project focuses on the archive of internationally renowned folklorists Iona (b. 1923) and Peter Opie (1918-1982). The Opies' landmark publications were based on information contributed by some 20,000 children from schools all over Britain, in response to three surveys (c.1950&ndash;80), supplemented by the Opies&rsquo; own in-depth observation and sound recording, of a wide variety of games and forms of play. The Opie archive at the Bodleian includes the survey responses, correspondence, and the Opies&rsquo; loose-leaf research files. At present, this collection can only be searched by physically looking through the papers. It is consequently little used, even by specialists. At the same time, even limited use results in wear and tear of a collection which is vulnerable to the possibility of damage through mishandling or misfiling.</p> <p>Our goal is threefold:</p> <ul> <li>One, to unlock this archive's full potential by creating a catalogue, and physically preparing the archive for a future digitisation project, which will permit creative uses of the content without endangering the original materials.</li> <li>Two, to publicise the archive in its usable form to a wide range of audiences and encourage increased and diverse use.</li> <li>Three, detailed scoping of digitisation possibilities in collaboration with intrerested academic partners<em>.</em></li> </ul>

Amount: £102,382
Funder: The Wellcome Trust
Recipient: University of Oxford

Urban animals, human livelihoods and health in the global south: a trans-species approach 10 Nov 2016

<p>Many of the urban poor in the global south rely on animals for their livelihoods.&nbsp; Yet complex relations between animals, informal livelihoods and health have received scant systematic theoretical and applied attention in the social sciences.</p> <p>&nbsp;</p> <p><em>Urban Animals</em> questions why the urban poor believe they need to keep animals, hypothesizing that these needs are structured by social, spatial and economic forces.&nbsp; It explores health implications emerging from these trans-species arrangements and the management responses they provoke.</p> <p>Combining ethnographic enquiry with analytics of comparative urbanisms, its goal is to develop concepts for understanding human-animal relations in megacities and their health implications in the global south.&nbsp; Central to this goal is to adopt a novel trans-species approach, moving away from anthropocentric leanings of urban studies and public health.&nbsp;</p> <p>&nbsp;</p> <p>This Seed Award will be used to conduct pilot and feasibility studies in New Delhi and Cape Town; collect preliminary data to underpin conceptual, methodological and comparative development; build/consolidate international academic and stakeholder partnerships; and develop collaborative research capacity.&nbsp;Its outputs will be a cross-continental interdisciplinary research consortium which will have generated concepts and evidence for a Wellcome Collaborative Award.</p>

Amount: £49,845
Funder: The Wellcome Trust
Recipient: University of Oxford

Targeting malaria hotspots in Myanmar: An individual-based modeling approach 22 Nov 2016

<p>The epidemiology of malaria in Myanmar has been changing with its decreasing incidence in Myanmar, while there is also an urgent need to address emerging resistance to artemisinin. Current malaria control strategies are no longer enough to achieve elimination. New strategies, like targeting of malaria hotspots where transmission intensity exceeds the average, have been suggested both by studies and the WHO.</p> <p>Such targeted strategies has been implemented in Kayin, Myanmar. However, detection of hotspots using qPCR has been limited to randomly selected villages because of the financial and operational constraints. This could be optimized by a simulation model.</p> <p>The proposed project will develop an individual-based mathematical model to:</p> <p>- Understand/model the changing epidemiology of malaria as its incidence declines in Myanmar</p> <p>- Derive cost-effective strategy to identify and treat malaria hotspots&nbsp;in Kayin, Myanmar</p> <p>As inputs, the model will have census data, population movement, and malaria data from relevant sources to create a dynamic, synthetic population. Simulated individuals will have their own risk of infection, health behaviour and response to treatment which will influence the overall disease transmission dynamics. A corresponding mosquito model will drive the force of infection for humans. Several detection methods and treatment strategies will be simulated.</p>

Amount: £128,087
Funder: The Wellcome Trust
Recipient: University of Oxford

Livestock, Environment and People (LEAP) 06 Oct 2016

<p>Changes in the amount and type of animal-sourced food (ASF) we consume, and in the way they are produced, are critical drivers of global human health and environmental quality.&nbsp; The project will develop novel policy tools and interventions to allow more informed and effective action to be taken to maximise the health and environmental co-benefits of changes in ASF consumption.&nbsp; We shall build a quantitative food system model incorporating economic, health and environmental modules that will allow the effects of existing drivers and novel policy interventions to be assessed. We shall exploit unique epidemiological resources to provide new evidence about how different types of ASF affect health, and conduct experiments to develop new interventions to influence the consumption of ASFs and ASF substitutes.&nbsp; A social-science component will research how social norms and political economic factors affect the practicality and acceptability of interventions, and how this may be changed. &nbsp;The effects of different types of ASF production on climate change, water use and quality, and ecosystem functions will be measured and brought together for the first time.&nbsp; The project will develop a distinct work stream in China and engagement with multiple audiences will be integral to all its activities.</p>

Amount: £4,391,572
Funder: The Wellcome Trust
Recipient: University of Oxford

Future of Animal-sourced Foods (FOAF) 06 Oct 2016

<p>Changes in the amount and type of animal-sourced food (ASF) we consume, and in the way they are produced, are critical drivers of global human health and environmental quality.&nbsp; The project will develop novel policy tools and interventions to allow more informed and effective action to be taken to maximise the health and environmental co-benefits of changes in ASF consumption.&nbsp; We shall build a quantitative food system model incorporating economic, health and environmental modules that will allow the effects of existing drivers and novel policy interventions to be assessed. We shall exploit unique epidemiological resources to provide new evidence about how different types of ASF affect health, and conduct experiments to develop new interventions to influence the consumption of ASFs and ASF substitutes.&nbsp; A social-science component will research how social norms and political economic factors affect the practicality and acceptability of interventions, and how this may be changed. &nbsp;The effects of different types of ASF production on climate change, water use and quality, and ecosystem functions will be measured and brought together for the first time.&nbsp; The project will develop a distinct work stream in China and engagement with multiple audiences will be integral to all its activities.</p>

Amount: £947,700
Funder: The Wellcome Trust
Recipient: University of Oxford

Complex Urban Systems for Sustainability and Health (CUSSH) 06 Oct 2016

<p>The CUSSH programme will deliver strategically vital global research on the complex systemic connections between urban development and health. Based on transdisciplinary methods, it will develop critical evidence on how to achieve the far-reaching transformation of cities needed to address vital environmental imperatives for population and planetary health in the 21st century. <br />Its core components include:</p> <ul> <li>a systematic review of evidence on potential solutions;</li> <li>the development and application of methods for tracking the progress of cities to towards sustainability and health goals;</li> <li>the development and application of models to assess the impact on population health, health inequalities, socio-economic development and environmental parameters of alternative urban development strategies to support policy decisions;</li> <li>iterative in-depth engagements with stakeholders in partner cities in low-, middle- and high-income settings, based on participatory methods, to test and deliver the implementation of the transformative changes needed to meet local and global health and sustainability objectives.</li> </ul> <p><span>Through these steps, the project will provide transferable evidence on how to accelerate actions essential to achieving population-level changes in such areas as energy provision, transport infrastructure, green infrastructure, water and sanitation, and housing. Associated public engagement and training, based on principles of co-generation of research, will be embedded throughout.&nbsp;</span></p>

Amount: £149,988
Funder: The Wellcome Trust
Recipient: University College London

Unravelling the molecular complexity behind ocular maldevelopment 06 Dec 2016

<p><strong>Aim:</strong> Investigating the relationship between genotype, gene expression and phenotype of <u>m</u>icrophthalmia, <u>a</u>nophthalmia&nbsp;and ocular <u>c</u>oloboma&nbsp;(MAC), which collectively causes one-third of life-long blindness and severe visual impairment in children worldwide.</p> <p>&nbsp;</p> <p><strong>Research questions: </strong>What are the pathogenic variants underlying MAC? How do molecular subtypes correlate with phenotype and stratify clinical risk?&nbsp; What molecular pathways are involved in human eye development? What is the relationship between genotype and gene expression in microphthalmia?</p> <p>&nbsp;</p> <p><strong>Key goals and methodology:</strong></p> <ol> <li>Whole genome sequencing of 30 parent-offspring trios with isolated MAC and longitudinal phenotyping. Establish an international reference network to stratify a well-defined cohort to improve care pathways and future research.</li> <li>Temporal comparative analysis of DNA methylome (bisulfite conversion and Illumina Infinium EPIC BeadChips) and transcriptome (65 million reads per sample using Illumina HiSeq-2500) in the developing human eye between 4-9 weeks gestation.</li> <li>Model 3D human microphthalmic optic cups using iPSC technology with isogenic controls using CRISPR/Cas9 gene-editing. DNA methylome and transcriptome analysis to assess disruption of molecular pathways.</li> </ol> <p>&nbsp;</p> <p><strong>Outcomes:</strong> Establish a molecular framework for ocular maldevelopment. Identify drug targets and develop therapeutics. Improve genetic diagnosis, counselling and management. Elucidate shared molecular mechanisms between embryonic tissue fusion defects and late-onset visual sensory disorders.&nbsp;</p>

Amount: £1,133,875
Funder: The Wellcome Trust
Recipient: University College London

Using visual dysfunction to understand dementia in Parkinson’s disease 06 Dec 2016

<p>Dementia affects half of patients with Parkinson&rsquo;s disease (PD) but there are no robust measures to predict who is at highest risk. Visual hallucinations are highly distressing to patients and carers but are poorly understood. This Fellowship will use visuo-perceptual dysfunction to predict dementia and understand hallucinations in PD.</p> <p>I have developed a novel test using skewed images to detect visuo-perceptual deficits in Parkinson&rsquo;s patients. I have also developed a web-based platform to enable this and other visual tests to be accessed by large numbers of patients with PD.</p> <p>In this proposal I will use visual perceptual tests combined with neuroimaging over time to determine the sequence of visuo-perceptual deficits in PD. I will relate these to changes in hallucinations. I will use my web-based platform to identify clinical and genetic associations with visual deficits and determine their role in predicting dementia in PD.</p> <p>Goals</p> <p>1. Characterise changes in visuo-perception as PD progresses and correlate deficits with brain atrophy.</p> <p>2. Relate MRI structural connectivity changes with disease progression.</p> <p>3. Examine clinical and genetic associations of visual dysfunction in PD.</p> <p>4. Test whether transcranial stimulation can improve visuo-perceptual function in PD.</p> <p>5. Determine how visual hallucinations become distressing as PD advances.</p>

Amount: £1,223,282
Funder: The Wellcome Trust
Recipient: University College London

The role of BMP signalling in diseases of the motor unit 06 Dec 2016

<p>Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset, neuromuscular disease characterized by lower motor neuron degeneration as result of misfolding and accumulation of mutant Androgen Receptor (AR). In recent years this scenario of selective neuronal vulnerability has been challenged by the discovery that in SBMA, as in other diseases of the motor unit, skeletal muscle, rather than being a mere bystander of motor neuron degeneration, is primarily affected and therapies exclusively targeting muscle ameliorate the pathology in motor neuron while preventing the development of a neuromuscular phenotype in animal models. My goal is to elucidate the molecular mechanisms underlying the intrinsic contribution of skeletal muscle in SBMA pathogenesis. I will investigate the role of the Bone Morphogenetic Protein (BMP) signalling pathway in SBMA pathophysiology, testing the central hypothesis that failure to activate the protective BMP pathway in SBMA muscle in response to denervation causes primary muscle atrophy and affects motor neuron ability to cope with the stress posed by mutant AR. The rationale is to provide a molecular basis for the cell-autonomous and non-cell autonomous roles of muscle in the mechanisms of toxicity in SBMA and other diseases of the motor unit and to identify novel therapeutic targets.</p>

Amount: £1,048,938
Funder: The Wellcome Trust
Recipient: University of Oxford

Control and enzymatic activation of the APC/C ubiquitin ligase system 30 Nov 2016

<p>CDK1 and APC/C are two key regulatory enzymes controlling the cell division, growth, differentiation and death, through phosphorylation and ubiquitylation, respectively. Although it has long been apparent that phosphorylation modifies APC/C function, the challenges posed by the need for functional assays to study this control puts the elucidation of the molecular basis of phosphorylation control beyond our grasp. We have recently overcome these limitations with a pipeline that uses reconstituted recombinant APC/C in <em>Xenopus</em> cell free extracts to show how CDK1 activates the APC/C through coordinated phosphorylation of Apc3 and Apc1. We will now extend this pipeline with targeted assays that will determine how phosphatases regulate these phosphorylation events. Because we have found that the disordered loop domains of APC/C subunits are targets for both post-translational modifications (PTMs) and interacting partners, including protein phosphatases, we will study how the loop domain controls the APC/C. Cell cycle specific and stress-dependent PTMs and binding proteins will be identified and we will determine their impact upon APC/C-dependent ubiquitylation. This approach of combining high throughput reconstitution mutated apo-APC/C in extracts from which any component of interest can be depleted offers a unique opportunity to gain an unprecedented insight into APC/C function and control.&nbsp;</p>

Amount: £1,547,248
Funder: The Wellcome Trust
Recipient: University College London

Explaining Language Outcome and Recovery After Stroke (ELORAS) 30 Nov 2016

<p>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&rsquo;s inherent potential and prior experience.&nbsp; 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 &nbsp;structural imaging measures.&nbsp; 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.</p>

Amount: £2,701,886
Funder: The Wellcome Trust
Recipient: University College London

Endothelial cell behaviours in vascular health and disease 30 Nov 2016

<p>At the interface between blood and tissues, vascular endothelial cells (ECs) provide signalling hubs for vascular adaptation to physiological needs. Quiescent ECs form a non-thrombotic surface that facilitates the exchange of gases, molecules and cells between blood and tissues, but they respond to hypoxia-induced signals with vascular expansion and regulate leukocyte extravasation in response to injury. Our unpublished observations indicate that the cell surface receptor neuropilin 1 (NRP1) relays signals from the extracellular environment to the endothelial nucleus to enable such context-dependent responses. Thus, we hypothesise that NRP1 integrates growth factor and extracellular matrix signalling with gene transcription programmes to balance EC behaviours that enable vascular growth and to prevent the senescent and proinflammatory endothelial phenotype common to many chronic diseases. To determine how vascular growth and homeostasis depend on NRP1-mediated pathways, we will investigate novel mechanisms by which NRP1 conveys signals for tissue vascularisation, protects ECs from premature senescence and regulates gene transcription for vascular growth and homeostasis. The knowledge gained will significantly advance our understanding of how extracellular signals are integrated with gene regulation to control EC behaviour, and will likely uncover pathways for therapeutic intervention in diseases with vascular dysfunction.</p>

Amount: £1,436,838
Funder: The Wellcome Trust
Recipient: University College London

Organization of large neuronal populations during behavior 30 Nov 2016

<p>Behavior arises from the coordinated function of vast numbers of neurons across the brain. However, we lack answers to fundamental questions concerning this coordinated function. How is the activity of multiple brain areas globally structured? How does this global structure relate to the firing of local neuronal populations? And what is the role of this coordination in producing animal behavior?</p> <p>&nbsp;</p> <p>Until recently, these questions were barely answerable: one could only record from tens or hundreds of neurons, and during single behaviors. &nbsp;They are now answerable, thanks to new, powerful techniques available in the brain of the mouse: optical recordings of over 10,000 neurons simultaneously, optical and ultrasound measures of mesoscopic activity in multiple brain regions, next-generation electrode arrays that record thousands of neurons across multiple areas, and temporally targeted optogenetic manipulations.</p> <p>&nbsp;</p> <p>We will combine these techniques to understand how brain-wide neuronal populations operate in the mouse brain during different behavioral conditions: rest, passive sensory stimulation, locomotion, sensory discrimination, and goal-directed navigation. These data will provide an unprecedented view on the neuronal-level organization of populations across the brain during behavior.</p>

Amount: £3,642,870
Funder: The Wellcome Trust
Recipient: University College London

The mechanisms of photoreceptor cell death 30 Nov 2016

<p>Problems of protein homeostasis (proteostasis) that lead to protein misfolding, improper traffic and aggregation are associated with many forms of neurodegeneration. The neurodegeneration retinitis pigmentosa (RP) offers an excellent paradigm to study why proteostasis is critical for neuronal function and survival. Rhodopsin mutations cause dominant RP and disturb proteostasis, yet the underlying disease mechanisms and effective therapies remain elusive. I will exploit recent advances in gene editing technology and stem cell biology to produce new animal and patient derived models of the most common rhodopsin mutations in the UK. I will use these to address my key goals, i) to define any common disease mechanisms between the different classes of mutation, and ii) identify new therapeutic approaches for rhodopsin RP. I will use a combination of genetic and chemical manipulation of the major cell stress and degradation pathways, and identify the partner proteins of rhodopsin mutants using unbiased proteomic analyses. These complementary studies will be based on a series of interlinked hypotheses to determine how rhodopsin mutations disturb protein homeostasis and if this can be restored. The findings will have broader implications not only for other forms of retinal degeneration, but also neurodegenerative disease where proteostasis is disturbed.&nbsp;</p>

Amount: £1,529,466
Funder: The Wellcome Trust
Recipient: University College London

Characterising extreme innate immune response phenotypes informative for disease using a functional genomics approach 30 Nov 2016

<p>The overall aim is to define and characterise extreme innate immune response phenotypes in order to gain insights into the functional alleles driving such differences between individuals; biological consequences in terms of gene regulation, cellular function and disease; and opportunities for therapeutic intervention. Key goals are (1) to analyse existing transcriptomic and expression quantitative trait mapping datasets for primary monocytes activated by lipopolysaccharide (endotoxin) or interferon-gamma from a large cohort of healthy volunteers to identify extreme responders (aggregated and gene level), using genetics to resolve functional alleles then validate and establish functional consequences including through chemical probes; (2) to use genome editing to conduct high-throughput screens in human induced pluripotent stem cell derived monocytes complementing the genetic data; (3) to define key nodal genes and networks for drug target discovery and prioritisation; and (4) to characterise prioritised genes and functional alleles modulating gene transcription and epigenetic regulation relevant to disease. Anticipated outcomes are improved understanding of pathophysiology in immune-mediated disease notably sepsis; exemplars to the field of how to establish mechanism for functional alleles involving regulatory genetic variants; improved interpretation of genome-wide association studies; novel nodal points involving TLR and related pathways as drug targets; and better drug target prioritisation.</p>

Amount: £1,575,666
Funder: The Wellcome Trust
Recipient: University of Oxford

Transforming brain recordings with next-generation probes 30 Nov 2016

<p>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 &ldquo;Neuropixels&rdquo; 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 (<strong>Aim 1</strong>). 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 (<strong>Aim 2</strong>). 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 (<strong>Aim 3</strong>). 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.</p>

Amount: £2,287,189
Funder: The Wellcome Trust
Recipient: University College London

Transforming brain recordings with next-generation probes 30 Nov 2016

<p>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 &ldquo;Neuropixels&rdquo; 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 (<strong>Aim 1</strong>). 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 (<strong>Aim 2</strong>). 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 (<strong>Aim 3</strong>). 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.</p>

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

Using parasite population genomics to improve understanding of malaria epidemiology 30 Nov 2016

<p>This collaborative project will use genomic approaches to characterise demographic flux and evolutionary trends in the malaria parasite population.&nbsp; Using novel methods for parasite genome sequencing that are suitable for large-scale field applications, we will perform longitudinal studies of parasite population genomics at multiple locations with different transmission intensities in Africa and Southeast Asia, and we will examine the clinical and epidemiological correlates of population genomic variables under a range of ecological settings.&nbsp; We will develop statistical and computational approaches to use longitudinally sampled genome sequencing data to construct spatial maps of parasite demography and examine how this changes over time. We will promote collaboration between experts on population genomics, geospatial mapping and mathematical modelling to use these data to inform and improve epidemiological models of malaria transmission. &nbsp;Our overarching goal is to establish the practical and analytical foundations to use parasite genome sequencing to investigate the causes of epidemiological events such as resurgence and emerging drug resistance, and thus to assist in planning effective interventions.&nbsp;</p>

Amount: £3,989,275
Funder: The Wellcome Trust
Recipient: University of Oxford

The translational potential of mass spectrometry and next-generation sequencing in patients with central nervous system infections in Vietnam 22 Nov 2016

<p>Central nervous system (CNS) infections are devastating conditions worldwide, especially in low- and middle-income counties (LMIC). Clinical outcomes are dependent upon the rapid identification of the causative agent and instituting effective antimicrobial therapy, although the causative agent is only identified in &lt;50% of patients. Furthermore, Southeast Asia is highly susceptible to the emergence of novel and drug resistant pathogens. New diagnostic techniques are urgently required for rapid response to future outbreaks, and to improve patient outcomes.</p> <p>This Fellowship will focus on the translational potential of mass spectrometry and next-generation sequencing (NGS) in clinical diagnostics of CNS infections in Vietnam, and has three key goals:</p> <ol> <li>To determine whether Mass spectrometry of cerebrospinal fluid (CSF) will identify protein/peptide signatures associated with different infectious aetiologies.</li> <li>To determine whether NGS-based metagenomic analysis will identify a broad range of known/unknown pathogens in the CSF and improve upon current standard laboratory assays.</li> <li>To determine whether NGS can provide rapid, whole genome sequence-based prediction of antimicrobial susceptibility for <em>Mycobacterium tuberculosis</em> and <em>Streptococcus pneumoniae</em>. &nbsp;</li> </ol> <p>I aim to provide proof-of-principle that CSF proteomics- and NGS-based methods can improve upon the diagnostic assays currently available in hospital settings, especially in LMIC, and thereby potentially improve patient outcomes.</p>

Amount: £685,086
Funder: The Wellcome Trust
Recipient: University of Oxford