Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Current Filters

Recipients:
Broadfield Primary School
University of Cambridge
Amounts:
£500 - £1,000
Award Year:
2017

Results

Vacation Scholarships 2017 - University of Cambridge 16 Jun 2017

<p>Vacation Scholarships 2017 - University of Cambridge</p>

Amount: £21,500
Funder: The Wellcome Trust
Recipient: University of Cambridge

Master's Award in Humanities and Social Science 30 Jul 2017

<p>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;In my three essays, I will explore case studies of British biotechnology and bioethics since the 1960s. My first essay will investigate the history of organ donation regulation in the UK by focusing on two pieces of legislation: the Human Tissue Act of 1961 and the Human Organ Transplants Act of 1989, which aimed to regulate the procurement of cadaveric and live organ donors, respectively. Next, I will examine the British Biotech controversy of the 1990s. After exaggerating their production of marimastat for cancer treatment, the company lost accreditation and eventually dissolved. I will explore this public controversy using as a key source the episode in BBC2&rsquo;s series <em>Blood on the Carpet </em>that recorded the politics behind the company&rsquo;s downfall as a key source. Finally, I will examine the use of Foucauldian ideas in the rise of British bioethics in the 1960s. Focusing specifically on the emergence of what, following Ludwik Fleck, I call the bioethical thought collective, I hope to expand on Daniel Wilson&rsquo;s work by analyzing how the collective&rsquo;s philosophical ideals deployed and engaged with Foucault&rsquo;s concept of biopower. Pursuing these research topics will expand my understanding of current British bioethical debates and American-British policy differences.</p>

Amount: £28,440
Funder: The Wellcome Trust
Recipient: University of Cambridge

Exploring Disorganised Attachment: Unravelling Developmental Pathways and Outcomes using Data Mining 30 Jun 2017

<p>Disorganised attachment is an important assessment of infant mental health, introduced by Main and Solomon (1990). Disorganisation is thought to result from an infant having in some way experienced trauma within the context of the relationship with their caregiver (e.g. observing severe domestic violence). Infants classified as disorganised have an&nbsp;elevated risk of psychological problems, most notably conduct disorders (Fearon et al. 2012).</p> <p>&nbsp;</p> <p>The possibility of a finer-grained measure emerged out of archival research, under Duschinsky's New Investigator Award,&nbsp;on&nbsp;the original Berkeley dataset from which disorganised attachment was first identified.&nbsp;</p> <p>&nbsp;</p> <p>As a result of the significant stakes for research and clinical practice, we have been offered unprecedented access to a remarkable longitudinal dataset to explore a) how the finer-grained measure fares against the standard construct in predicting a range of negative outcomes, and b) whether particular forms of disorganisation have specific antecedents.&nbsp;Given that the goal is exploratory and the array of relevant measures is extensive, data mining will be used rather than hypothesis-testing. The research offers the prospect of a significant&nbsp;transformation of research in this area. Three focus groups with clinicians will be conducted to facilitate clinical input and translation.&nbsp;</p>

Amount: £25,976
Funder: The Wellcome Trust
Recipient: University of Cambridge

Amulets and the material culture of healing 25 May 2017

<p>The goal of this project is to investigate how amulets represent varying forms of value and power across differing chronologies. The Science Museum's collection will allow me to comprehensively examine a diverse range of objects, and research different forms of medical, magical and scientific worth and potency unavailable by studying textual sources alone. This project will ask three questions:&nbsp;How do objects with both similar and antithetical social values&ndash;from the rare to the quotidian, the expensive to the ubiquitous&ndash;represent differing forms of remedial power?&nbsp;In which different ways do these amulets represent the patients' experience of illness and healing and how can we as historians and museum curators afford these objects &lsquo;voices&rsquo; without being anachronistic and jeopardising their original power?&nbsp;Finally, what material features have led to certain objects being considered as curative, prophylactic or apotropaic, and to what extent do function and potency depend on manmade and natural materials? This project will use these amulets to help answer important questions about European healing practices from medieval period to present day. A direct, material analysis of the objects and collections will elucidate the historical importance of these objects, and what they can contribute to our knowledge of health and healing.</p>

Amount: £15,523
Funder: The Wellcome Trust
Recipient: University of Cambridge

ISA-InterMine: accelerating and rewarding data sharing 06 Jul 2017

<p>There is a growing recognition that research should be carried out in an open fashion, making data available early and in a reusable form to maximise worldwide research output. However, fulfilling this promise requires front-line researchers to comply with current data management standards as required by the data policies of funders and journals. These are additional burdens to research that will give them little immediate return.</p> <p>&nbsp;</p> <p>Thus we propose to create a cloud-based, open-source, extensible data collection and presentation platform that will provide scientists with: (1) immediate reward for their annotation efforts through sharable data visualisation, integration outputs and exploration tools; (2) standardised web services to facilitate script-based data manipulation and analysis; (3) an easy-to-use pipeline for preparing their data for publication; (4) incentives to improve data quality, accessibility, and machine-actionability at the appropriate level of granularity; and (5) allow institutions and other parties to host the platform to ensure its availability and reliability.</p> <p>&nbsp;</p> <p>We will do this by building on the success and complementarity of the ISA tools suite (Oxford) and the InterMine platform (Cambridge) to make it quicker and easier to generate rich integrated dynamic web sites at single paper/lab scale up to consortium scale.</p>

Amount: £670,410
Funder: The Wellcome Trust
Recipient: University of Cambridge

Virtual Fly Brain 06 Jul 2017

<p>Neuroscience is accelerating: the capability to generate circuit level hypotheses is now matched with the ability to visualise, manipulate and record from individual neurons, in vivo. Drosophila, with its complex adaptive behaviors, powerful genetic toolkit and small nervous system, for which we will soon have complete connectomes, is uniquely placed to contribute to this work.</p> <p>&nbsp;</p> <p>Virtual Fly Brain (VFB) is a unique resource for Drosophila neuroscience, integrating disparate, large-scale datasets and linking them to curated literature and other resources. VFB works with international data providers and bioinformatics resources to ensure efforts are complementary, non-redundant, and make best use of resources.</p> <p>&nbsp;</p> <p>VFB users browse and query curated information from many sources to understand structure, function and relationships in the brain. Critically, VFB provides the data to generate circuit hypotheses and identify research tools to test them. This proposal continues this vital service and extends it to incorporate rich new data types. We will incorporate synaptic resolution connectomic data, develop bridging registrations to make it bidirectionally queryable from light level data. We will add phenotypic and transcriptomic datasets and enhance tools that enable researchers to find reagents. We will enable users to upload, view and query their own 3D datasets.</p>

Amount: £996,004
Funder: The Wellcome Trust
Recipient: University of Cambridge

‘Pre-embryos’ Revisited: a historical sociology of translational biology 02 May 2017

<p>This project will revisit the debates on human fertilisation and embryology that took place after the release of the Warnock report in 1984 and ended with the enactment of the Human fertilisation and Embryology Act in 1990. Firstly, it will ask how developmental biologist Dame Anne McLaren (1927-2007) used the scientific concept of the &lsquo;pre-embryo&rsquo; as a rhetorical device in the debates to make the case for the continuation of research. McLaren&rsquo;s role as the only research scientist on the Warnock Committee, but also in public debate and in the scientific community offers insight into the translational dimensions of human embryo research. Secondly, the research will explore the legacy of the term &lsquo;pre-embryo&rsquo; by asking practicing developmental biologists conducting research that begs for an extended limit on in vitro research on human embryos, to reflect on the term in order to suggest which lessons about biological translation can be taken from the debates in the 1980s, and to assess the usefulness of new scientific terms and concepts when engaging lay-audiences in scientific debates.</p>

Amount: £135,903
Funder: The Wellcome Trust
Recipient: University of Cambridge

Diagnosing Diagnosis: a multidisciplinary perspective 17 Jul 2017

<p>Diagnosis is at the heart of the medical encounter, but many features of making, communicating and recording a diagnosis remain poorly understood and little researched. Without greater understanding, we cannot provide adequate guidance to clinicians about what information to share with patients or adequate advice to patients about what questions to ask, and policy incentives to address problems with &lsquo;overdiagnosis&rsquo; or &lsquo;misdiagnosis&rsquo; are at risk of unintended consequences.</p> <p><strong>Key goals:</strong></p> <ol> <li>To examine the process of making, communicating and recording a medical (differential) diagnosis in the acute care setting;</li> <li>To examine institutional influences on the diagnostic process;</li> <li>To examine ethical and philosophical influences on making and communicating diagnoses;</li> <li>To establish an empirically based, ethically grounded framework for making, communicating and recording a diagnosis to improve patient outcomes on both individual and societal levels.&nbsp;</li> </ol> <p><strong>Methodology:</strong></p> <p>Qualitative methods including ethnography and interviews will be combined with medical records analysis and quantification of the reach and permanence of diagnostic labelling between health care settings. Integrated with this empirical work, ethical analysis will explore how the interplay between responsibility, uncertainty and trust affects the process and communication of making a medical diagnosis. This is emphatically multidisciplinary research which &nbsp;benefits from combining different perspectives and methodologies.</p>

Amount: £647,257
Funder: The Wellcome Trust
Recipient: University of Cambridge

Attachment and the transgenerational effects of loss, abuse and trauma: Exploring and testing classic ideas through historical analysis and developmental science 02 May 2017

<p>Since it was introduced by John Bowlby, attachment research has been among the most influential paradigms for understanding the social underpinnings of infant mental health and transgenerational mental health. However, an odd artefact of the way a major research instrument was constructed in the 1980s by Mary Main has meant that to date attachment research has largely treated loss, abuse, and trauma as essentially equivalent, despite their very different clinical implications. A multidisciplinary approach will be used to investigate these concepts and examine potential differences. Work Package 1 will comprise a critical re-examination of the concepts of loss, abuse and trauma&nbsp;in the published and unpublished works by John Bowlby and Mary Main, exploring their reflections on how these experiences might impact parenting. In Work Package 2, hypotheses elaborated in Work Package 1 will be tested using Individual Participant Data pooled from 59 attachment studies, representing 4,542 families. Work Package 3 tests explanations for differential effects of unresolved loss, abuse&nbsp;and trauma on parenting and child development using longitudinal data from 400 mothers and children. The study will shed new light on transgenerational mental health processes, and insights will be disseminated to professionals and families.</p>

Amount: £97,935
Funder: The Wellcome Trust
Recipient: University of Cambridge

21st Century Families: Parent-child relationships and children's psychological wellbeing 25 Jul 2017

<p>New pathways to parenthood have recently emerged that did not exist, nor had even been imagined, at the turn of the 21<sup>st</sup> century. Individuals who were previously unknown to each other have begun to meet over the internet with the purpose of having children together; transgender men and women have begun to have children through medically assisted reproduction; single heterosexual men have begun to use surrogacy to become single fathers by choice; and women have begun to use identifiable egg donors to have children. These emerging family structures raise new ethical, social and psychological concerns, particularly regarding the potentially negative consequences for children. The proposed research will provide empirical evidence from a multidisciplinary perspective on the social and psychological consequences for children of growing up in family arrangements involving non-cohabiting co-parents, transgender parents, elective single fathers and identifiable egg donors. In this emotive area of family life on which people often hold strong opinions, our aim is to challenge prejudice and assumption with evidence on the actual consequences &ndash; good, bad or neutral &ndash; for children. The ultimate goal of the proposed research is to increase understanding of diversity in family life and improve the lives of 21<sup>st</sup> century children.</p>

Amount: £1,552,401
Funder: The Wellcome Trust
Recipient: University of Cambridge

From Cures to Courts of Justice: The Medical Encounter and Social Order in Early Modern Spain 17 Jul 2017

<p>Early modern encounters have mainly been studied as transactions between individual sick people and their healers. This project shifts the focus by placing encounters within the communities that structured early modern lives and the practices and expectations of social order that shaped them. The variety of encounters that took place in the Catholic kingdom of Castile provides an ideal case study to establish this fresh perspective on the politics of health care. By combining trial records, tracts on medical etiquette and literary sources, the project explores how encounters intersected with the domestic, collective and religious order of close-knit urban and rural communities. It has three main goals:</p> <p>1) To reveal which assumptions about norms and stability guided the encounters.</p> <p>2) To explore how in practice encounters fostered or disrupted social stability. Subsidiary goals are: to show how communities monitored, and communicated about, healing practices; to discuss how, as encounters unfolded, religious discipline intersected with other facets of social order.</p> <p>3) To assess the informal and formal strategies, including legal, by which communities managed controversial encounters. Subsidiary goals are: to understand how an encounter turned into a legal dispute; to evaluate which short- and long-term consequences this process had for communities.</p>

Amount: £147,847
Funder: The Wellcome Trust
Recipient: University of Cambridge

In vivo mechanisms of epithelial tissue morphogenesis 11 Jul 2017

<p>Understanding how a tri-dimensional tissue is built from the genetic blueprint is a key frontier in biology. In addition to genes known to be important in specific aspects of morphogenesis, physical constraints and properties play a major role in building tissues. In this proposal, I aim to understand how the genetic inputs integrate with the mechanical properties of the cells and tissues to produce form. To investigate this, we study the early development of the <em>Drosophila</em> embryo. We have found previously that actomyosin-rich boundaries play an important role in two fundamental and conserved morphogenetic phenomena, axis extension and compartmental boundary formation. We have also found that an extrinsic force contributes to axis extension. We will build on these findings by first investigating how the actomyosin-rich boundaries form and how they might repair genetic patterns during axis extension. Second, we will ask how, during compartmentalisation, they control the planar orientation of cell division and also epithelial folding. Finally, we will examine the impact of actomyosin-rich boundaries and extrinsic forces on epithelial tissue mechanics. Our approaches will be interdisciplinary, combining genetic, quantitative and&nbsp;<em>in silico&nbsp;</em>analyses&nbsp;to find novel and universal morphogenetic rules.</p>

Amount: £1,440,082
Funder: The Wellcome Trust
Recipient: University of Cambridge

Biomechanics of Ciliated Tissues 11 Jul 2017

<p>Many of the paradigmatic events in embryonic development involve geometric or even topological rearrangements of tissues in response to mechanical forces generated within them. While these processes are familiar and much studied from genetic and biochemical perspectives, there is a striking contrast between the great depth of such biological detail and the glaring lack of quantitative <em>mechanical</em> understanding of the forces and responses involved. &nbsp; We propose to close the theory-experiment loop in specific, carefully chosen examples of these problems, to gain a quantitative understanding of the underlying biomechanics. &nbsp;We seek to solve three outstanding problems: (i) the link between cell shape changes and cell sheet morphology as found in gastrulation, neurulation, and related problems in embryogenesis; (ii) the mechanism of generation of cilia orientational polarity in tissues; (iii) the origin of metachronal wave formation in carpets of cilia.&nbsp; The research will combine state-of-the-art light-sheet microscopy, micromanipulation, high-speed imaging and microfluidics with emerging theoretical tools for understanding complex geometrical transformations of tissues and the stochastic nonlinear dynamics of eukaryotic flagella.</p>

Amount: £1,656,325
Funder: The Wellcome Trust
Recipient: University of Cambridge

Entry, innate sensing and replication of enteropathogenic caliciviruses. 11 Jul 2017

<p>Our overarching aim is to gain insights into the biology of enteropathogenic caliciviruses,&nbsp;focusing on the fundamental aspects that have remained elusive to date: &nbsp;viral entry into target cells, the interplay with the host innate response and the recruitment of host-cell co-factors that support replication.&nbsp;&nbsp;<strong>Having significantly improved the culture systems for human noroviruses and developed reverse genetics, we now have the first opportunity to study human norovirus replication in a physiologically relevant system.</strong> We will focus on three areas:</p> <p>&nbsp;</p> <p><strong>1.&nbsp;C-type lectin receptors (CLRs)</strong>: We have found that CLRs may work in concert with blood group antigens to allow norovirus infection.&nbsp;We will further dissect the role of CLRs in the norovirus life cycle.</p> <p>&nbsp;</p> <p><strong>2. Innate responses to infection</strong>: We have found that type I/III interferons&nbsp;restrict norovirus replication but&nbsp;that infection induces the COX-2/PGE pathway to promote replication. We will dissect the response to infection in the organoid system and characterise a novel virus-encoded regulator of the NF-kB system.</p> <p>&nbsp;</p> <p><strong>3. Trans-acting factors:</strong>&nbsp; We will examine their role of a number of host factors (VapA/B, Squle&nbsp;and PI4Kalpha) in norovirus replication and expand this study to an undertake an unbiased analysis of the human norovirus replication complex.&nbsp;</p>

Amount: £2,204,335
Funder: The Wellcome Trust
Recipient: University of Cambridge

Mechanisms of epithelial polarity in flies and mammals 11 Jul 2017

<p>Apical-basal polarity is essential for all aspects of epithelial cell function and loss of this polarity is a hallmark of cancer. We have recently found that the endodermal epithelium of the <em>Drosophila</em> adult midgut polarises by a different mechanism from other <em>Drosophila</em> epithelia and may provide a good model for endodermal epithelia in mammals. This proposal aims to understand how polarity is generated in both epithelial types. Firstly, we will examine how the canonical polarity complexes polarise the secretory epithelium of the <em>Drosophila</em> follicle cells. We will investigate how Cdc42 is activated to define the apical domain; we will use optogenetics and super-resolution microscopy to investigate the dynamics and composition of polarity complexes; and we will analyse how cortical polarity organises the microtubule cytoskeleton through the lateral polarity factor, Par-1. Secondly, we will perform clonal screens to identify essential epithelial polarity factors in the <em>Drosophila</em> midgut and characterise their functions. To test whether these factors play conserved roles in mammals, we will knock out their orthologues in mouse intestinal organoids. This research will reveal the fundamental mechanisms that polarise different epithelial types, which is an essential prerequisite for understanding epithelial function and how it is perturbed in diseases like cancer.</p>

Amount: £3,611,874
Funder: The Wellcome Trust
Recipient: University of Cambridge

Whole genome sequence based analysis of genetic variation and genome evolution 11 Jul 2017

<p>DNA sequencing is a core technology for modern biomedical science, and our ability to sequence genomes with ease and use that information efficiently is still unfolding. I propose first to build new bioinformatics data structures and software to map sequence data, call genetic variants, and integrate phasing and imputation, scaling to millions of samples with high accuracy and making best use of new long read sequencing technologies. These will be based on sequence variation graphs and haplotype panels over them, effectively exploiting already-discovered genetic variation in the population. Second I will develop new statistical methods to infer the evolutionary history of genome sequences to identify ancestral populations, model gene flow between them, and date and place mutations into them. I will apply these methods to modern and ancient samples to elucidate Eurasian and African human population history. Finally, I will apply these methods to new data I collect from the Lake Malawi adaptive radiation of over 500 species of cichlid fish, to infer the evolutionary relationships in the radiation, test models of speciation, and identify genes involved in cranio-facial adaptation. These studies will empower future use of sequencing data in biomedicine, and advance our understanding of genome structure and evolution.</p>

Amount: £3,027,662
Funder: The Wellcome Trust
Recipient: University of Cambridge

Molecular characterisation of antibiotic tolerance in Mycobacterium tuberculosis 11 Jul 2017

Tuberculosis, caused by Mycobacterium tuberculosis still causes 1.8 million deaths per year and takes months to years to treat. Long treatment times are due to subpopulation(s) of bacteria that, although genetically susceptible, are not killed effectively by antibiotics – termed antibiotic tolerance. Understanding mechanisms of antibiotic tolerance is the key to shortening treatment times for tuberculosis. We have recently shown that mycobacteria use the essential amidotransferase GatCAB to regulate rates of specific errors in gene translation and that mistranslation is both necessary and sufficient for tolerance to rifampicin – the most important anti-tuberculous drug. However, the precise molecular mechanisms by which GatCAB and the mycobacterial translation machinery control fidelity are not understood. We have also recently identified further mechanisms which contribute to rifampicin tolerance. We now propose to determine the mechanism by which GatCAB modulates mistranslation rates. We also propose three complementary forward genetic screens to a) comprehensively identify the pathways that regulate mycobacterial translational fidelity; b) employ bacterial genome-wide association studies to identify mutations that influence rifampicin tolerance in clinical isolates, and c) use saturating transposon insertion mutagenesis and deep sequencing to identify mycobacterial genes that cause differential rifampicin susceptibility in a murine model of antibiotic treatment.

Amount: £1,195,984
Funder: The Wellcome Trust
Recipient: University of Cambridge

Fundamental mechanisms controlling human energy homeostasis 11 Jul 2017

<p>Obesity and associated diseases such as type 2 diabetes, cardiovascular disease and some cancers represent a significant health burden. My overall aim is to identify new therapeutic strategies for severe obesity. Using extensive genetic and clinical data on unique cohorts of individuals at both extremes of the weight distribution (severe obesity and thinness), we will comprehensively map the molecular networks that maintain energy homeostasis and their disruption in disorders of weight regulation. Building on our previous work, we will focus on dissecting cellular mechanisms that converge on leptin-melanocortin signalling using human stem-cell derived hypothalamic neurons. In human studies, we will characterise the effects of specific pathways on eating behaviour, energy expenditure and substrate utilisation. By uncovering the fundamental mechanisms that control human energy homeostasis, our goal is to identify and validate control points that can be targeted to improve outcomes in obesity associated diseases.</p> <p>&nbsp;</p>

Amount: £3,582,289
Funder: The Wellcome Trust
Recipient: University of Cambridge

Fundamental mechanisms controlling human energy homeostasis 11 Jul 2017

<p>Obesity and associated diseases such as type 2 diabetes, cardiovascular disease and some cancers represent a significant health burden. My overall aim is to identify new therapeutic strategies for severe obesity. Using extensive genetic and clinical data on unique cohorts of individuals at both extremes of the weight distribution (severe obesity and thinness), we will comprehensively map the molecular networks that maintain energy homeostasis and their disruption in disorders of weight regulation. Building on our previous work, we will focus on dissecting cellular mechanisms that converge on leptin-melanocortin signalling using human stem-cell derived hypothalamic neurons. In human studies, we will characterise the effects of specific pathways on eating behaviour, energy expenditure and substrate utilisation. By uncovering the fundamental mechanisms that control human energy homeostasis, our goal is to identify and validate control points that can be targeted to improve outcomes in obesity associated diseases.</p> <p>&nbsp;</p>

Amount: £50,000
Funder: The Wellcome Trust
Recipient: University of Cambridge

Structural cell biology of transport vesicle and organelle biogenesis 11 Jul 2017

<p>Integral membrane protein cargo are constantly moved in coated tubular/vesicluar carriers between the cell's organelles and its limiting membrane in order to maintain membrane identity and function. That these transport processes are of fundamental importance is reflected by the fact that ~30% of mammalian proteins are either components of the vesicle/tubule transport machinery or are its cargo.&nbsp; Coated vesicular/tubular carrier formation including cargo selection requires the interplay of a network of peripheral membrane proteins and membrane components including phospholipids, small GTPases, docking proteins and the cargo itself. The coat must also prepare and facilitate the carrier for fusion with its target. AP2, AP3, COPI and retromer/VARP based coats along with their accessory/regulatory factors are vital for producing a fully functional endosomal system. We will use a combination of X-ray crystallography, NMR and the fast developing techniques of single particle cryoEM and cryo electron tomography allied with biochemical/biophysical studies to formulate theories concerning the architecture, assembly routes and control/regulation of the formation of these four key tubular/vesicular transport carriers. Specific function abolishing mutations designed on the basis of these studies will allow us to test and further explore our theories in cells using a&nbsp; wide range of in vivo techniques.</p>

Amount: £3,445,099
Funder: The Wellcome Trust
Recipient: University of Cambridge