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

Currency:
GBP
Recipients:
Cardiff University
University of Oxford

Filter By

Recipient Region
Recipient District
Funding Organizations
Recipient Organizations (clear)
University of Oxford (1,569) University of Cambridge (1,282) University College London (1,143) Imperial College London (748) University of Edinburgh (718) Guy's and St Thomas' NHS Foundation Trust (565) King's College London (519) University of Manchester (443) University of Bristol (420) London School of Hygiene & Tropical Medicine (391) University of Glasgow (335) University of Dundee (312) University of Liverpool (307) The Royal British Legion (300) Newcastle University (299) University of Birmingham (298) Cardiff University (259) University of Leeds (235) King's College London (218) Queen Mary University of London (190) University of Warwick (182) University of York (177) Liverpool School of Tropical Medicine (173) University of Nottingham (173) University of Sheffield (171) Merched Y Wawr (161) University of Exeter (153) University of Leicester (149) Barnardo's (141) The Guide Association (139) The Scout Association (131) University of Southampton (125) Alzheimer's Society (115) Cruse Bereavement Care (113) University College Dublin (108) Church of England Children's Society (107) University of Aberdeen (107) Institute of Cancer Research (100) Birkbeck University of London (96) The National Trust for Places of Historic Interest or Natural Beauty (95) The National Childbirth Trust (90) Queen's University Belfast (89) University of Sussex (88) St George's University of London (87) Wellcome Trust Sanger Institute (86) Education Services - Headquarters (85) Volunteering Matters (83) University of St Andrews (78) Medical Research Council (73) National University of Ireland Galway (72) See Less

Results

Delivering Care Through AI Systems 08 May 2018

For this project, I aim to examine 4 issues. First, I will consider whether introducing machine learning (ML) systems requires a revision of the ‘standard of care’ for clinicians, by understanding the moral permissibility of using second-hand information (from ‘black box’ systems) and whether practitioners’ medical expertise justifies judgments about such systems. Second, given the possibility of ML systems systematically underserving groups that are underrepresented in the training data, I will consider accounts of distributive justice to operationalize ‘equal access to care’. Third, to address the disagreements between clinicians on how to trade-off risks in clinical choices, I will catalogue the factual, rational, and moral sources of this disagreement to yield a principled method of evaluating these trade-offs. Finally, I will weigh the potential harms and gains from deploying AI systems in healthcare so that certain ethical and legal arguments don’t deprive society of the good such systems can provide. Key goals: To represent the ethical concerns in deploying AI systems over the appropriate standard of care, ensuring equal access to care, and representing reasoning about risk trade-offs. To balance these concerns against the benefits of such a deployment. To deliver practical ethical guidance to healthcare policy-makers and AI system-builders.

Amount: £140,538
Funder: The Wellcome Trust
Recipient: University of Oxford

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

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.

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

Structural and functional dissection of the RH5:CyRPA:RIPR complex required for erythrocyte invasion by Plasmodium falciparum 05 Dec 2016

Invasion of human erythrocytes by Plasmodium falciparum is essential for parasite replication and occurs before the symptoms of malaria. It is a complex process involving many parasite surface proteins. Recently, one of these, RH5, emerged as the leading vaccine candidate to target the ‘blood stage’ of the parasite life cycle. RH5 interacts with erythrocyte basigin while monoclonal antibodies that prevent binding also prevent erythrocyte invasion. Immunization with RH5 protects animal models from parasite infection and RH5 enters human clinical trials in 2016. We already determined the structure of RH5 bound to basigin and inhibitory antibodies: a major goal of my investigator award. On the merozoite surface, RH5 forms part of a larger complex, interacting with CyRPA, RIPR and a fourth, GPI-anchored component. RH5, CyRPA and RIPR are each essential for erythrocyte invasion and are targets of antibodies that block invasion. Despite this, their functions are unknown, leaving a major gap in our understanding of erythrocyte invasion by Plasmodium falciparum. We will now undertake structure-function studies of the RH5:CyRPA:RIPR complex. Working with Simon Draper, we have developed eukaryotic expression systems to produce RH5, RIPR and CyRPA. We assembled them into a complex and showed that this is elongated, homogeneous and rigid by negative stain electron microscopy. Monoclonal antibodies targeting each component havebeen generated. We will now determine the structure of this recombinant RH5:CyRPA:RIPR complex using electron cryo-microscopy, and investigate where inhibitory monoclonal antibodies bind.

Amount: £150,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Molecular mechanisms of HIV-1 restriction by capsid-sensing host cell proteins 05 Apr 2017

Infections by retroviruses, such as HIV-1, critically depend on the viral capsid. Many host cell defence proteins, including restriction factors Trim5alpha, TrimCyp and MxB, target the viral capsid at the early stages of infection and potently inhibit virus replication. These restriction factors appear to function through a remarkable capsid pattern sensing ability that specifically recognizes the assembled capsid, but not the individual capsid protein. Using an integrative and multidisciplinary approach, I aim to determine the molecular interactions between the viral capsid and host restriction factors, TrimCyp and MxB, that underpin their capsid pattern-sensing capability and ability to inhibit HIV-1 replication. Specifically, I will combine cryoEM and cryoET with all-atom molecular-dynamics simulations to obtain high-resolution structures and atomic models of the capsid and host protein complexes (in vitro), together with mutational and functional analysis as well as correlative light and cryoET imaging of viral infection process (in vivo and in situ), to reveal the essential interfaces in their 3D organization for HIV-1 capsid recognition and inhibition of HIV-1 infection. Information derived from our studies will allow to design more robust therapeutic agents to block HIV-1 replication by strengthening the pattern recognition feature.

Amount: £1,476,229
Funder: The Wellcome Trust
Recipient: University of Oxford

Genomic medicine and statistics 30 Sep 2017

Not available

Amount: £2,580,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Structural studies of bacterial nucleic acid transport proteins 31 Jan 2017

Horizontal gene transfer contributes to genetic plasticity in bacteria and is of great clinical relevance as it contributes to the spread of antibiotic resistance genes. One mechanism of horizontal gene transfer in bacteria is transformation. While the phenomenon of transformation has been known for many decades, little is known about the mechanistic steps of exogenous DNA uptake into bacterial cells. The most obvious problem is how the DNA gets past the cell envelopes. ComEC is believed to be the protein that forms an aqueous pore that allows transport of DNA into the cytoplasm through the bacterial plasma membrane. The protein represents a novel transport protein, and no structural and very little functional information is available. The aim of the project is to structurally and functionally characterize ComEC proteins using modern protein expression and screening techniques, advanced structural approaches (X-ray crystallography, cryo-electron microscopy) and functional studies (fluorescence microscopy, biophysics), in order to build a model for DNA transport across the plasma membrane into the cytoplasm.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

KDEL Receptor Stuctural Determination & Biochemical Characterisation 31 Jan 2017

This project aims to characterise the KDEL receptor (KDELR) structurally, biochemically and biophysically. The KDELR is a membrane protein resident in the cis-golgi, where it binds the K-D-E-L amino-acid motif present on resident ER proteins, which have been transported to the Golgi via bulk flow. Once KDELR binds cargo, it initiates transport back to the ER via COPI mediated vesicles, where it releases its cargo, ostensibly because of the differing pH. The molecular mechanisms concerning the actions of the KDELR are largely elusive and would be greatly aided by the structural determination of the KDELR, as well as the structures and characterisations of its interactions with native cargos. Furthermore, KDELR has been predicted to be a GPCR, but does not appear to share homology with proteins in the family. However, distant homology to the SWEET family of sugar transporters has been found, suggesting these ‘receptors’ are in fact transporter like proteins. Furthermore, this project has the potential to involve live cell imaging experiments (in collaboration with Prof. Francis Barr) to test hypothesis borne from the structural and biochemical data.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Investigating the role of Kv1.6 in pain pathways 31 Jan 2017

Kv1.6 is a member of the Shaker-like Kv1 potassium channel protein family. Widely expressed in the nervous system, these channels have delayed outward rectifier properties and evidence indicates that they act to suppress action potential firing. In the field of neuropathic pain, of which neuronal hyperexcitabilty is a common hallmark, these channels are of interest as their malfunction or downregulation may contribute to the disease pathophysiology. While less is known of Kv1.6 than other subunits of the same family, it has recently been reported that this channel is upregulated following nerve injury, signifying some role for Kv1.6 during the time after injury. Pharmacological inhibition at this stage indicates a functional role for Kv1.6 in restoring hypersensitive pain thresholds somewhat towards more normal values. Having already conducted some preliminary research on the Kv1.6 knock-out mouse, I will employ various in vivo, ex vivo and in vitro techniques from behavioural chronic pain models to electrophysiology, calcium signalling and gene/protein expression analysis in order to further probe the importance of this channel in health and disease, and to determine its sites of action amongst the various neuronal populations along somatosensory/pain pathways in the peripheral and/or central nervous system.

Amount: £29,760
Funder: The Wellcome Trust
Recipient: University of Oxford

Pancreatic Alpha Cells and Glucagon Secretion in Mouse Models of Diabetes 31 Jan 2017

Type 2 diabetes (T2DM) is characterised by insufficient insulin secretion, insulin resistance and dysregulated glucagon secretion. The processes underlying alpha-cell dysfunction in T2DM, leading to elevated glucagon secretion and exacerbated hyperglycaemia, remain poorly understood. With evidence indicating that electrical activity, Ca2+ signalling and hormone secretion occur somewhat independently of each other (at different times, under different conditions), the nature of alpha-cell signal transduction is unclear. We will generate mice expressing the Ca2+ sensitive fluorescent indicator (GCaMP) under the glucagon promoter and will measure Ca2+ oscillations in isolated islets alongside electrical activity. Following fluorescence activated cell sorting (FACS) of whole islets, electrical activity and Ca2+ signalling of isolated alpha-cells will be performed to assess the impact of loss of paracrine effects on alpha-cell function. mRNA and protein expression will also be measured in isolated cells to verify the specificity of marker expression. Also all experiments will be conducted in diabetic mice and littermate controls to assess the effect of hyperglycaemia and beta-cell dysfunction on alpha-cell physiology. These studies, conclusively characterising the nature of stimulus secretion coupling in pancreatic alpha-cells, and its disintegration in T2D, will provide valuable insight into the process underlying pancreatic dysfunction and possible opportunities to reclaim glycaemic control.

Amount: £39,978
Funder: The Wellcome Trust
Recipient: University of Oxford

Understanding the cellular and molecular basis of epithelial migration using the Angiomotin mutant 31 Jan 2017

Epithelial morphogenesis is a complex process involving tissue-level integrity and dynamically coordinated morphogenetic change. The visceral endoderm (VE) in the mouse embryo is one such tissue that undergoes morphogenesis required for embryonic development. In angiomotin (amot) mutants, there is a characteristic abnormal furrowing in the anterior VE accompanied by aberrant apical build up of actin. This leads to reduced displacement of anterior VE cells and embryonic lethality. We do not understand the cellular and molecular basis for abnormal cell migration in this mutant, nor what proteins AMOT interacts with in this context. To address these questions, I will initially make detailed quantitative observations of cell behaviour by analysing light sheet and confocal microscopy data, using automated cell segmentation and tracking approaches I am developing. I will explore actin dynamics using FRAP and laser ablation on mutant and wild-type embryos. To understand the molecular pathway through which AMOT regulates epithelial cell behaviour, I will use a phosphoproteomic approach to identify interacting proteins using wild-type and amot mutant ES cell-derived embryoid bodies. Select interacting proteins will be tested for their role using small molecule inhibitors where available, or CRISPR mediated mutagenesis in ES cells and mice.

Amount: £31,026
Funder: The Wellcome Trust
Recipient: University of Oxford

Early lineage decisions during mouse gastrulation 31 Jan 2017

Diversification of mesoderm and endoderm subtypes occurs at the outset of mouse gastrulation as epiblast cells migrate through the primitive streak (PS). The underlying inductive signals, gene-regulatory networks, and epigenetic modifications that direct lineage diversification at this early stage remains ill-defined. The aim of this project is to dissect the molecular mechanisms that underpin cell fate diversification, as cells egress the PS, by investigating the function of T-box transcription factors (TF), Eomesodermin (Eomes) and Brachyury (T). Eomes and T are expressed in the PS and Eomes is required for specification of cardiac mesoderm (CM) and definitive endoderm (DE). Single cell lineage tracing and RNA-seq experiments will be completed to define the potency and heterogeneity of Eomes and T expressing progenitors. The functional role Eomes plays in haematopoiesis will also be investigated using multiple gain and loss of function experiments. Finally, we will investigate context dependent Eomes binding sites and interacting partners. Eomes tagged mouse embryonic stem cells (mESC) will be differentiated into CM or DE progenitors and with them we will perform ChIP-Seq, RNA-Seq and immunoprecipitation-mass spectrometry(IP-MS). The experiments proposed will help resolve the functional and molecular roles T and Eomes play during early stages of lineage diversification.

Amount: £45,812
Funder: The Wellcome Trust
Recipient: University of Oxford

Functional dissection of a single enhancer sequence at the mouse a-globin locus 31 Jan 2017

Enhancers are cis-regulatory DNA elements that bind transcription factors and chromatin remodelers and drive expression of target genes in a spatiotemporal context. Despite their importance in cell fate specification in development and differentiation, up to now enhancers have largely been studied in assays that are poor predictors of their in vivo requirement and function. In this project, I will probe enhancer sequence requirements for gene regulation in situ, using the mouse a-globin locus as a model. In order to directly dissect the critical sequences, I will first produce a mouse where a-globin expression is driven by a single element (R2) by deleting the other four endogenous enhancers (R1, R3, R4 and Rm). After validating this mouse for its chromatin environment and transcriptional output, I will perform a high-throughput screen of modified R2 enhancer sequences for transcriptional output using an ES cell in vitro haematopoietic differentiation system. From these results I will select three mutant sequences for molecular characterisation in vivo. Resulting data from primary mouse tissues will provide insight into transcription factor binding interdependence, recognition site ‘grammar’ and how binding affects the enhancer-promoter interactions critical for transcription.

Amount: £37,583
Funder: The Wellcome Trust
Recipient: University of Oxford

Dissecting Polo kinase recruitment to the centrosome 31 Jan 2017

Polo kinase is an important cell cycle regulator and it is essential for the correct assembly of centrosomes, major cell organisers. Centrosomes are formed by a pair of cylindrical centrioles surrounded by pericentriolar material (PCM). Polo controls PCM assembly (at least in part through Cnn phosphorylation) and also centriole disengagement and assembly. How Polo is recruited to centrioles and centrosomes is mysterious. During my rotation I have obtained evidence that the PCM protein Spd-2 is necessary for Polo recruitment to centrosomes. During my project I aim to characterise if Polo binding to Spd-2 is necessary for Cnn phosphorylation and correct PCM organisation, what happens when Spd-2 cannot bind Polo and what upstream regulators facilitate this interaction. Furthermore, I aim to identify the other centriole/centrosome proteins involved in Polo recruitment. To do this, I will make use of biochemical assays and advanced microscopy techniques, coupled with fly genetics and a powerful mRNA injection assay to rapidly test the effects of different mutants in fly embryos. Ultimately, I hope to be able to describe in molecular detail which proteins are phosphorylated by which kinases to allow Polo to be recruited to fulfil its many functions at the centrioles and centrosomes.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Inducing and disrupting white matter plasticity 31 Jan 2017

Recent evidence has shown that dynamical changes in white matter underlie the learning of motor skills. This has been observed both in humans with Diffusion Tensor Imaging (DTI, Schulz et al., 2009) and in rodents with histology (Sampaio-Baptista et al., 2013). These findings raise questions on which conditions are necessary for WM plasticity induction and how the plasticity they induce is modulated by genetic factors. Can an artificial induction of white matter plasticity in humans lead to behavioural changes, even without actual motor experience? To answer this question, the first aim of my DPhil will be to induce white matter plasticity at rest; more specifically, I will attempt to do so through fMRI neurofeedback, and will monitor the outcome with DTI and other myelin-specific MRI modalities. Given that white matter is often implicated in psychiatric disorders, a second question regards whether genes related to mental health conditions (in this case, NR1), can influence how white matter responds to learning, and possibly underlie a deficient or maladaptive response. Therefore, the second aim of my DPhil will be to investigate whether WM plasticity is affected in a mouse model of white matter-specific knockout of NMDA receptors.

Amount: £83,102
Funder: The Wellcome Trust
Recipient: University of Oxford

The role of regulatory T cells in immunity to malaria 31 Jan 2017

In malaria vaccine trials conducted in the target population of semi-immune people from endemic African countries, vaccine immunogenicity is sometimes substantially reduced compared to European malaria-naïve participants. This could result from the suppression of vaccine-induced immune responses by regulatory T cells (Tregs) acquired through prior malaria infections, however there are few studies in man which have previously explored this. Using samples from controlled human malaria infection studies in semi-immune Kenyan individuals, we will investigate how Tregs affect natural immunity to infection and see if increased Treg responses correlate with vaccine efficacy following malaria challenge in participants with varying prior exposures to malaria. We will also directly compare the effect and induction of Tregs in different pre-erythrocytic candidate vaccines and adjuvants to understand how vaccine-specific effects might affect Treg responses. Additionally, we will investigate if malaria-induced Tregs affect responses to other childhood vaccines. Single cell transcriptomic analysis using the Fluidigm platform will be employed to explore the phenotype and functional heterogeneity of Tregs. This will provide insight into the mechanisms by which Tregs are involved in immunity to malaria. This work will have important implications for the design and evaluation of malaria vaccines for use in endemic populations.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Not just a virulence factor: capsule biology across the Neisseria genus 31 Jan 2017

This project seeks to address the relatively unexplored topic of the genetics, function and evolutionary history of the Neisseria polysaccharide capsule, beyond its established role as a virulence factor in Neisseria meningitidis (Nme). This will be achieved by examining capsular types not associated with disease, both from Nme, and capsules recently discovered in the commensal Neisseria species. The first goal is to complete genetic and phenotypic characterisation of the novel commensal capsular types. Once this is established, a key goal is to seek comparisons between these novel capsules and those of Nme within the coding sequences and regulatory regions, and at the structural level. I also plan to address the question of what the role of capsule is in colonisation and transmission, given that it most likely was not selected for its virulence properties. Finally, I seek to build a clearer history of the acquisition and evolution of capsule in Neisseria. This will bring forward new insights into the roles of capsule in normal, healthy colonisation of the nasopharynx, both by Nme and the strictly commensal Neisseria species. This work may also have implications for our interpretation of Nme dynamics and the rare transition to a state of disease.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

The role of β-amyloid in cognition in normal and APP knock-in mice 31 Jan 2017

Working hypothesis: modulation of beta-amyloid (Abeta) production (in the absence of APP overexpression) in mice will lead to changes in brain network activity and cognitive function. Our understanding of dementia pathogenesis has been heavily influenced by the amyloid cascade hypothesis. However, progress is hampered by the fact that (1) little is known about the normal function of Abeta and (2) current mouse models of amyloid pathology rely on over-expression of human APP mutations. APP over-expression alone causes synaptic and cognitive changes that are independent of Abeta production. We propose to examine the role of normal Abeta production in synaptic plasticity and cognition and to characterize a novel knock-in mouse model of amyloid pathology (Saito et al., 2014; the NL-F mouse). We will examine cognitive changes in NL-F mice during aging to establish a profile of brain network changes. We will test the effects of steric hindrance of Abeta production on memory by using an antibody (2B3) that binds across the beta-secretase cleavage site in both NL-F and WT mice. Analysis of memory function will be accompanied by assessment of network activity (c-fos expression), brain metabolite profile (MR-Spectroscopy) and APP cleavage products (using standard biochemical assays) in NL-F and WT mice.

Amount: £31,128
Funder: The Wellcome Trust
Recipient: Cardiff University

Understanding mechanisms that drive pain perception in early human development 11 Jul 2017

Pain in infancy has negative long-term consequences and its prevention is a clinical priority, but adequate treatment requires mechanistic understanding of the structural and functional development of human nociceptive circuitry. Recent scientific and technological advances provide insights into how noxious information is transmitted to the infant brain, providing a platform to ask how intrinsic brain network connectivity and the environment affect noxious-evoked brain activity, behaviour and ultimately pain perception in the developing infant nervous system. The fellowship goal is to understand the mechanisms that drive and modulate pain perception in early human development. I will ask whether inherent differences in how the brain behaves at rest influence variability in noxious-evoked activity, and will determine how this relationship is altered by environmental factors and pathology. I will establish how the development of structural and functional network connectivity alters noxious-evoked brain activity, and influences the dynamic relationship between brain activity and behaviour. I will translate this mechanistic understanding into clinical practice by conducting a clinical trial of an analgesic (fentanyl) during a minor surgical procedure, and will establish whether our newly-developed measures of noxious-evoked brain activity are suitable for use in infant analgesic dose-finding studies.

Amount: £60,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Enhancing the WT MOP Vietnam's Engagement Programme 30 Aug 2017

In 2015 the WT Major Overseas Programme Vietnam was awarded a renewal of its Core funding. The MOP has a history of successful public engagement, funded through International Engagement awards and from industry sponsorship. However, with the introduction of the Provisions for Public Engagement funding scheme, we applied for funding for engagement at an institutional level, enabling us to create a 5-year strategic plan for developing engagement capacity within the MOP and in the region. Now, 20 months into the award, we reflect on activities to date, and plan strategically for the second part of the programme. The 5-year public engagement programme includes a schools engagement programme (SEP) and a capacity building programme (CBP), both of which have proved to be very successful and highly valued by our local government and school partners. The third focus has been to develop researcher capacity for engagement – through small grants and offering training and mentoring. We have had a good uptake of these ‘seed awards’ from MOP researchers and increasing interest in engagement from researchers at local institutes in Vietnam. Schools Engagement: The SEP has been very successful (http://www.mediafire.com/file/td3kaomtu9t7ia7/Application.7z), in particular: afterschool science clubs; weekly science articles in a children’s magazine; science theatre; and lab visits enabling young people to interact with scientists. The SEP has also included ‘I’m a scientist, Get me out of here’ - a competition linking children and scientists, run with Gallomanor UK (https://imascientist.org.uk) (https://www.youtube.com/watch?v=n--SJOtFm1w). Capacity building: The CBP was developed in recognition that much of the ‘front-line’ contact with patients and communities enrolled in clinical trials or cohort studies is from hospital or government study staff. In response we have started a CBP to train and support hospital health care workers (HCMC), community-based data collectors (Nepal) and local vets (in provinces where we conduct research on zoonosis). As the funding for the IAS project and other awards come to an end, we need additional funding to support the current PE team. This application is for additional staff salary costs and to run PE workshops to develop engagement capacity across the region.

Amount: £343,289
Funder: The Wellcome Trust
Recipient: University of Oxford

Assessing the anticancer properties of Biocyanin SLH 31 May 2018

Haemocyanins are oxygen-carrying proteins found in the haemolymph of molluscs and gastropods. They are of interest to biotech and medical research as strongly immunogenic carrier proteins, for making antibodies to conjugated peptides and for use as cancer vaccines. In addition, direct application of haemocyanin to tumours has been shown to produce an anticancer effect, and haemocyanins from several species including keyhole limpet have shown promise in the treatment of bladder cancer, colon cancer and melanoma. Particularly striking are their lack of toxicity and adverse effects. Recently, Mikota PLC have developed protocols for the purification of a new haemocyanin, Biocyanin SLH, from the slipper limpet Crepidula fornicata. The main aim of our proposal is to test the potential of Biocyanin SLH as an anticancer agent, by incubating it with a panel of cancer cell lines and assessing its ability to induce cell death. In addition, we will investigate the signalling pathways involved in the anticancer action of Biocyanin SLH, determining whether cell death occurs via apoptosis or necrosis, and analysing cellular production of stress molecules. Finally, we will label Biocyanin SLH with a fluorescent dye to track its interaction with cells using confocal microscopy. Keywords: haemocyanin, cancer, cell death.

Amount: £0
Funder: The Wellcome Trust
Recipient: Cardiff University