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Recipients:
University of Oxford
Award Year:
2016

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Results

Burden of Zika virus in different South East Asian populations with febrile illness. 30 Sep 2016

<p>Our planned studies will identify if ZIKV is a current and neglected problem in three SE Asian populations located in Thailand, Vietnam and on the Thailand Myanmar border.&nbsp; Although ZIKV is reported to be endemic in Asia its prevalence and true significance in South East Asia is not well characterised.&nbsp; Transmission of ZIKV Myanmar has not yet been reported, there have only been two confirmed cases recently reported in Vietnam and there are only seven published confirmed cases of ZIKV infections in Thai residents (these were reported by the Thai Ministry of Public Health in 2015).&nbsp; There are several cases of confirmed ZIKV infections from travellers returning from Thailand, indicating that ZIKV is an under and/or misdiagnosed infection in this country.&nbsp; Further work is therefore urgently required. This is important not only for local public health planning, but also from a global health perspective as travellers to and from these regions may be at risk of infection with associated complications and/or pose a transmission risk to na&iuml;ve populations.</p>

Amount: £20,000
Funder: The Wellcome Trust
Recipient: University of Oxford

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

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

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

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

Transient Complex Formation in Nanodroplets 09 Nov 2016

<p>Networks of molecular complexes play a fundamental role in biology. Transient interactions often regulate these networks and thus targeted interference offers possibilities for therapeutical intervention.</p> <p>Capturing these elusive complexes is far from trivial. Many are only present at low concentrations because of low-affinity, low solubility or high toxicity. Only a few have been captured and characterised.</p> <p>The physical chemistry of nanodroplets offers a way to enhance the formation of such biological complexes. Droplet populations can be created containing copies of different molecules and combinations of molecules in a statistical distribution. Controlled shrinkage of the droplets by evaporation slowly increases the effective concentration and drives energetically favoured interactions between trapped molecules. The complexes can then be structurally characterised by mass spectrometry, electron microscopy, and flash imaging with X-ray free-electron lasers. I plan to study two complexes: the poorly understood Rubisco - Rubisco-activase complex at the centre of plant carbon fixation, and the FANC core complex, where mutations cause DNA repair malfunctions, resulting in cytopenia, developmental defects, and tumor predisposition.</p> <p>The nanodroplet technology I will develop will make such hitherto difficult to study transient complexes of medical and biotechnological importance accessible to structural analysis.</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Utilising snake endogenous toxin inhibitors for the development of improved antivenom treatments 09 Nov 2016

Snake envenoming causes significant annual mortality, predominantly in the developing world. Currently the only effective treatment is antivenom, which is produced by hyperimmunising large animals with crude venom, and then extracting and purifying the antibodies raised against the snake proteins. This method requires keeping and maintaining large numbers of livestock, a key contributor to the high cost. Furthermore, the efficacy of antivenom is completely dependent on the venom sample(s) utilised for production, and the animal-derived antibodies can cause unwanted immunogenic effects in the patient, such as anaphylaxis. This project aims to make steps towards developing new antivenom treatments by utilising the endogenous toxin inhibitors used by snakes to protect themselves from their own venom. First, both the toxin and toxin inhibitor repertoire of 5 species of venomous snake will be elucidated using multi-'omic' technologies. Candidate inhibitors will be expressed in human cell lines, and subsequently tested experimentally to determine their efficacy in neutralising venom effects which cause the most life-threatening pathology. This method will revolutionise the antivenom field, and pave the way to developing treatments which are more cost effective, have fewer side effects, require no live animals, and have a greater and wider efficacy in treating snakebite.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Knowledge-driven analysis of image-based genetic screens using deep learning 09 Nov 2016

<p>Characterising gene functions is important for understanding life at the molecular level, and has a great impact on pharmacological and biomedical studies. Genetic screens that utilise High Throughput Imaging (HTI) have proved to be a powerful tool for studying gene functions by monitoring phenotypic changes in genetically modified cells. Challenges in analysing HTI datasets have significantly hindered knowledge discovery from such rich datasets. As HTI datasets are now acquired on a routine basis, there is a great need for generalisable analysis methods.</p> <p>Deep learning has revolutionised computer vision as it can automatically extract features and classify raw images without the need for any image preprocessing. I will develop deep learning methods to automatically discover cellular phenotypes and infer gene functions based on phenotypic similarity. I will build an integrative framework that utilises Functional Annotations (FAs) from various biological databases to annotate and classify images. I will apply these methods to five genome-wide datasets to predict tissue-specific gene functions based on the phenotypes of various cellular structures. <em><u>The outcome of this work will be robust and generalisable HTI analysis methods that associate phenotypes to gene functions using deep learning as well as the discovery of novel gene functions and associated phenotypes.</u></em></p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Understanding the interaction between Dengue virus and mosquito C-type lectins on the molecular level 09 Nov 2016

<p>The mosquito-borne virus Dengue constitutes an enormous burden on global human health. It is transmitted through the bite of the yellow fever mosquito <em>Aedes aegypti</em>. Recent studies have identified a family of proteins termed mosGCTLs that bind Dengue and promote infection of the mosquito. This attachment has been associated with an interaction between mosGCTLs and Dengue glycan moieties.</p> <p>I will elucidate, at the molecular level, how mosGCTL proteins recognize and attach to Dengue and can thus facilitate infection enhancement. This will be addressed structurally at atomic resolution (via crystallography and cryo-EM) and in the whole organism through validation in live mosquitoes.</p> <p>Key goals:</p> <p><strong>(1)&nbsp;&nbsp; </strong>Elucidation of which carbohydrates are bound by mosGCTLs using microarray screening, followed by co-crystallization and structure solution.</p> <p><strong>(2)&nbsp;&nbsp; </strong>Biophysical and structural characterization of the interaction between mosGCTLs and Dengue glycoproteins as well as whole virus. Here, I will make use of <em>in vitro</em> binding assays, providing a quantitative readout of interaction strengths.</p> <p><strong>(3)&nbsp;&nbsp; </strong>Cryo-EM single particle reconstruction of Dengue virus decorated with mosGCTL proteins to gain a holistic view of attachment to the icosahedral virus.</p> <p><strong>(4)&nbsp;&nbsp; </strong>Functional targeted mutagenesis studies with <em>Aedes aegypti</em> mosquitoes to investigate how our molecular level data translates into nature.</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Dissecting the antibody response to Plasmodium falciparum-infected erythrocytes 09 Nov 2016

<p>The antibody response against <em>Plasmodium falciparum</em>-infected erythrocytes (IEs) has been associated with protection against malaria, but the characteristics of this response at the monoclonal antibody level remain an open question. We have recently developed a high-throughput platform to isolate monoclonal antibodies against IEs that allowed us to identify novel LAIR1-containing antibodies that target RIFINs on the IE surface (Tan et al. 2016, <em>Nature</em>). Here, we propose to use this technology to interrogate the immune response of well-characterized malaria-exposed Malian individuals against IEs at the monoclonal antibody level. We plan to: a) compare the responses of naturally protected and non-protected individuals to identify potential signatures of protection, b) isolate antibodies that broadly target late-stage IEs and identify novel conserved antigens as malaria vaccine candidates, and c) study the repertoire of LAIR1-containing antibodies in Malian individuals. We believe that this plan is feasible, as we have obtained preliminary data suggesting that several Malian plasma recognize the majority of late-stage IEs and that a sizable proportion (5-10%) of these individuals possess LAIR1-containing antibodies. From this work, we hope to identify aspects of the antibody response that protect malaria-exposed individuals, potentially including broadly reactive antibodies against conserved IE antigens.</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Human sensitivity to short-wavelength light in non-image-forming vision: Toward a mechanistic understanding of the impact of blue light on sleep and circadian rhythms 09 Nov 2016

<p>Short-wavelength (blue) light takes priority in many functions associated with the non-image-forming (NIF) visual system, including pupil size and regulation of melatonin secretion. The human retina contains two short-wavelength sensitive photoreceptors: the blue-sensitive (S) cones (~440 nm) and the recently discovered photopigment melanopsin (~480 nm) expressed in a subset of retinal ganglion cells. Previous research has focused on the melanopsin contributions to NIF responses, but very little is known about how S cones contribute to and interact with melanopsin in these functions. Using the method of silent substitution which allows for the selective isolation of photoreceptor classes and by studying patient groups with S-cone anomalies, we will study the S cone and melanopsin inputs into pupil control and circadian mechanisms. In Aim 1, S cone and melanopsin inputs into the pupil will be characterised in controls and S-cone patients and related to sleep-wake actigraphy. In Aim 2, the spatial topography of S cone and melanopsin pupil inputs will be characterised using a novel spectral-spatial modulator. In Aim 3, S cone and melanopsin inputs into melatonin suppression will be characterised.&nbsp;In short, we will systematically characterise the receptor mechanisms that mediate the effect of short-wavelength light on circadian regulation in humans.</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

A dynamic approach to sensory processing in autism 09 Nov 2016

<p>The importance of sensory symptoms in autism is clear, but we do not yet understand why they occur. Previous research has concentrated on the end-point of sensory processing, failing to consider the dynamic process and confounding multiple stages leading to atypical responses. It is therefore unclear whether autistic individuals show altered accumulation of sensory evidence and/or altered decision bounds.</p> <p>&nbsp;</p> <p>This Fellowship will characterise better sensory processing in autism, with three objectives. First, I will pinpoint the mechanisms of sensory processing differences by quantifying sensory and&nbsp;decisional parameters and their relationships with action. Second, I will investigate how these parameters relate to everyday sensory symptoms in autism. Third, I will assess whether co-occurring symptoms moderate sensory processing differences in autism.</p> <p>&nbsp;</p> <p>I will use a model-based cognitive neuroscience approach. Autistic and typical children will make decisions on sensory stimuli while electroencephalography (EEG) is recorded. I will use hierarchical drift-diffusion models to jointly model behavioural and neural data to identify the components of sensory processing affected in autism. I will relate these components to parent-reported sensory symptoms and co-occurring symptoms. I will use Bayesian statistics to ensure the robustness of my findings. The findings will help to guide the design of future interventions.</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

The fate of multidrug tolerant bacteria: from single cells to microbial communities. 09 Nov 2016

<p>Many bacterial infections cannot be cured, even when caused by a pathogen that is not resistant to antibiotics. Central to this effect is the presence of a subpopulation of phenotypic variants called persisters, which enter a dormant state and can survive exposure to a broad range of antibiotics, causing recurrent and chronic infections.</p> <p>Persistence can be triggered by a variety of mechanisms, but it is unknown if these different mechanisms lead to the same cell state, and the same tolerance to antibiotics. Because persister cells are rare they are difficult to study with bulk assays. I will use microfluidics and quantitative fluorescence microscopy of&nbsp;<em>Escherichia coli</em><em> cells</em>&nbsp;to investigate how persistence states differ from one another in their gene expression and their tolerance to antibiotics. I will study how these cells revive from their dormant state, and at what point they become susceptible again.</p> <p>Chronic infections are often associated with biofilm formation, and increased antibiotic tolerance. By imaging persisters within bacterial colonies, I will establish if biofilms directly afford protection against antibiotic treatment, or rather if biofilms simply prevent removal of existing persister cells, allowing them to repopulate after antibiotic treatment finishes.&nbsp;</p>

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

All-optical interrogation of neural circuits during behaviour 26 Oct 2016

<p>Neural circuits display complex spatiotemporal patterns of activity on the millisecond timescale. Understanding how these activity patterns drive behaviour is a fundamental problem in neuroscience. To address this challenge, I have recently introduced a novel approach that combines simultaneous two-photon calcium imaging and two-photon targeted optogenetic photostimulation with the use of a spatial light modulator (SLM) to provide 'all-optical' readout and manipulation of the same neurons <em>in vivo</em>. I propose to probe the neural code in mouse barrel cortex during sensory-guided behavioural tasks by using this approach to uncover the underlying mechanisms of decoding and encoding of information by ensembles of neurons. I will train mice to make perceptual decisions based on quantitative control of cortical activity, as well as perturb neural activity in somatosensory cortex while animals are performing discrimination tasks using their whiskers. I can perform decisive tests of theoretical models describing the neural code by assessing the spatiotemporal pattern of activation required in somatosensory cortex to drive a behavioral response. These experiments will shed light on how many neurons with which functional signature are minimally sufficient to subserve a percept.</p>

Amount: £1,320,200
Funder: The Wellcome Trust
Recipient: University of Oxford

Real-time genetic cartography of viral epidemics 26 Oct 2016

<p>Predicting the course of an epidemic <em>following</em> its emergence remains one of the greatest challenges in infectious disease control. Although rapidly evolving viruses frequently threaten global public health, uneven surveillance efforts can obfuscate predictions of virus dynamics across local, regional and global scales. Genomic epidemiology is currently being revolutionized by the &ldquo;real-time&rdquo; sequencing of whole virus genomes in the field within days. Yet empirical datasets are often biased or hampered by limited analytical tools, potentially biasing inferences of viral dynamics and hindering predictions useful for outbreak control. To address these problems, I propose to develop a framework, termed &lsquo;<em>genetic cartography</em>&rsquo;, aimed at unifying the evolutionary analysis of viral genomes with medical surveillance data, high-resolution geographic measurements, and real-time human mobility data. The proposed research will deliver a statistical framework that unifies genetic, epidemiological and cartographic data in order to: 1) determine the impact of ecological and epidemiological drivers on the <em>historical</em> spread of RNA viruses across spatial scales, mobility networks and social groups; 2) incorporate metrics of human movement to infer <em>present</em> patterns of virus diversity and transmission; and 3) combine real-time genetic and mobility measures to deliver accurate <em>future</em> predictions of virus movement and disease burden.<strong></strong></p>

Amount: £668,899
Funder: The Wellcome Trust
Recipient: University of Oxford