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Results

How gay are your genes? 23 Jan 2006

How gay are your genes? "How gay is your genes?" is a science engagement project working with lesbian, gay and bisexual community in North East England, with the aim of promoting awareness and debate about the life sciences. Phase one commenced in 2004, with Lisa Matthews holding workshops and giving talks about genetics to gay community groups, and has been funded by COPUS. More than 300 individuals have participated to date in discussions of science, genetic research in general, and claims about genetic factors in sexual orientation in particular. We believe that this is the first science engagement project targeted at lesbian, gay and bisexual people. Phase two will commence in Autumn 2005, and will involve deeper work with a smaller group of lesbian and gay people, giving them the opportunity to hear from visiting speakers - for example, Professor Nancy Roughgarden, Professor Jenny Kitzinger, Dr Su Stenhouse - and to develop creative writing responses to genetics. The current People award application, will add a visual arts element to this innovative outreach project. Predrag Pajdic, a contemporary video artist, who is gay and has a gay identical twin, will work with Lisa Matthews and the gay community participants to develop artwork reflecting the responses and concerns which gay people have expressed about genetic research on sexuality. Pajdic's artwork will be exhibited in Newcastle's Hatton Gallery, alongside creative writing produced during the outreach workshops, to a broad audience - general public as well as gay community. Versions of the artworks and supporting material will also be available to a global audience via a website.

Amount: £20,700
Funder: The Wellcome Trust
Recipient: Newcastle University

Dissecting and disrupting Epstein-Barr virus transcription initiation and elongation during latent infection. 09 Feb 2006

This research will test the hypothesis that the switch from W to C promoter usage during initial EBV infection represents a switch from non-processive transcription to EBNA 2-activated CDK9-dependent processive transcription necessary for the efficient production of the long primary transcript and the establishment of latency. We will also investigate whether the requirement for CDK9 for the efficient activation of transcription by EBNA 2 makes the anti-cancer drug and CDK9 inhibitor, Flavopiridol, an effective anti-EBV agent. Additional studies will further dissect the way in which pol II phosphorylation is regulated by EBNA 2. Key goals 1. Determine whether EBNA 2 stimulates transcriptional elongation in addition to initiation. 2. Determine whether EBNA 2 activated transcription can be blocked using Flavopiridol. 3. Dissect how pol II phosphorylation is regulated by EBNA 2.

Amount: £254,448
Funder: The Wellcome Trust
Recipient: University of Sussex

The Imp2 mRNA binding protein: Roles in morphogenesis and differentiation of the mammalian inner ear. 20 Oct 2005

The inner ear develops from the otic placode, a specialised patch of neuroectoderm adjacent to the developing hindbrain. A major goal is to understand the molecular mechanisms that convert this patch of cells into the complex adult structure. IGF signalling is associated with inner ear development, but how inner ear IGF activity is controlled is not known. Previously we isolated the Igf2 mRNA binding protein, Imp2, and have shown it is expressed in different sensory epithelia during development, including the inner ear. In this project we will use gain and loss of function approaches in transgenic mice to determine the function of Imp2 in inner ear development. We will test the hypothesis that Imp2 is a key regulator of IGF activity, controlling morphogenesis and differentiation in the developing inner ear. Key Goals: Determine whether Imp2 regulates localised differential growth of cells in the otic epithelium Determine whether Imp2 affects hair cell differentiation Determine the effects of Imp2 on IGF1 & IGF2 expression Determine whether Imp2 regulates otic neuroblast proliferation and/or migration Determine the fate of Imp2 expressing cells in the mature inner ear Investigate the association of Imp2 with hair cell repair/regeneration

Amount: £231,619
Funder: The Wellcome Trust
Recipient: University of Sussex

Critical edition (with introduction, translation and commentary) of the Hippocratic treatise De Affectionibus. 10 Nov 2005

The treatise De Affectionibus ?????Peri pathôn), henceforth Aff., is a nosological work of about 60 pages Greek text (in the Littré-numeration), which already in antiquity was transmitted as a part of the 'Hippocratic Corpus'. Aff. is unique among the 'Hippocratic writings' in that it presents itself as a manual for lay people (not physicians). It provides a systematic discussion of diseases and their treatment. It then discusses a number of dietetic modes of treatment (foods, drinks, baths etc.) applied to a variety of diseases. It also refers several times to a discussion of drug treatment and drug preparation. The author of the work is unknown, and its date can only be established approximatively.No comprehensive critical edition of this important work exists; nor is there anything remotely aspiring to a modern scholarly commentary. The aim of this project is to produce such a critical edition of Aff., which will be based on an exhaustive study of the whole manuscript and printed tradition. Moreover, the Greek text will be accompanied by an English translation and a commentary in which the work will be placed within the intellectual context of the time. This edition will be published in the prestigious series Corpus Medicorum Graecorum of the Berlin-Brandenburg Academy of Sciences.

Amount: £147,999
Funder: The Wellcome Trust
Recipient: Newcastle University

Vacation Scholarships 2008. 27 May 2008

Not available

Amount: £10,080
Funder: The Wellcome Trust
Recipient: Newcastle University

Knowledge, Ethics and Representation of Medicine and Health - Historical Perspectives. 24 Apr 2007

This project aims to increase our understanding of the ways in which, from classical antiquity until the present day, medical knowledge and practice have been defined, established and validated, professionally institutionalised and ethically justified, and communicated and represented to a variety of audiences through a range of different textual and visual media. It will apply these questions to a number of different periods in the history of Western (and partly also non-Western) medicine, with particular emphasis on the mind-body interface and to the areas of gender and sexuality; and it will take due account of the social, geographical, institutional and environmental aspects of healthcare provision. Methodologically, it will do so through historical analysis of textual and visual sources in their social and cultural contexts, as well as demographic, archaeological and palaeopathological methods of research. The specific intended outcomes of the project are (a) scholarly publication s; (b) public engagement activities; (c) training of research students and nurturing of a new generation of scholars in the history of medicine; (d) increasing convergence between medicine and the humanities, both at student and at professional level.

Amount: £374,656
Funder: The Wellcome Trust
Recipient: Newcastle University

MA in History and Philosophy of Science and Medicine and MA in the History of Medicine. 31 Aug 2007

The right to health and medical care is included in the universal declaration of human rights. (Article 25, 1) Throughout history however, many people have been denied these rights. Human experimentation, such as experiments carried out in concentration camps during the Second World War demonstrate a total neglect of basic human rights. In such cases people are viewed upon and treated as less than human, suffering a violation of body and mind. Research into the area of medical experimentation would include: Reasons for medical experimentation; Discoveries / medical breakthroughs in the field of medicine as a result of such experimentation; and Implications of such discoveries. I would be interested to see if there have been any long term medical benefits which can be seen as a result of human torture. Would these have been discovered were it not for the pain endured by the victims? Clarification of the term experimentation is necessary. Medical torture is another term that is often used when describing the experimentation on unwilling human subjects. This aspect of bodies being used involuntarily is also relevant in death. For example, cases in the early 19th century saw victims murdered and their bodies sold to anatomy schools as a profit making exercise. Consider not only medical discoveries as a result of deliberate experimentation but also more indirect 'experimentation' such as the testing of human endurance through slavery.

Amount: £20,803
Funder: The Wellcome Trust
Recipient: Newcastle University

Computational and psychophysical studies of polarity effects in human visual motion processing. 28 Jun 2007

There is currently one widely accepted computational model of the earliest stages of visual motion processing in the brain, known as the motion energy model. Recent psychophysical and physiological results are inconsistent with the model, particularly with regard to responses dependent on the sign of luminance polarity. The proposal aims to develop and test a revised computational model of motion analysis. There are three key goals: 1) The first goal is to develop the revised model and establis h whether it can account for the basic capabilities of human motion perception. 2) Some perceptual effects are consistent with motion processes that respond to both signs of contrast polarity, others are consistent with processes that respond to only one sign of contrast polarity. The second goal is to determine whether the revised model can accommodate both kinds of effect. Predictions will be generated and tested in a series of psychophysical experiments. 3) Perceptual adaptation is a promin ent feature of motion processing, but previous models do not incorporate adaptation. The third goal is to establish whether the revised model provides an adequate explanation of perceptual adaptation.

Amount: £126,654
Funder: The Wellcome Trust
Recipient: University of Sussex

Characterisation and alleviation of post-operative pain in laboratory rats. 06 Feb 2007

Millions of laboratory rodents in Europe and North America undergo painful surgery annually. In most cases pain could be alleviated with appropriate analgesics treatment(s), however analgesics are either rarely used, or given at arbitrary dose rates and times. Our inability to assess pain is the primary reason for this, so we urgently need to know: How much pain the common surgical procedures cause? How long does the pain last? Which drugs are effective in alleviating pain? The s olution is to develop measures of post-operative pain. This project will use multiple measures (behaviour, endocrine and nociceptive responses) to refine our abilities to assess pain following different surgical procedures in rats. By utilising a unique automated behaviour recognition system we will rapidly refine our pain assessment capabilities in rats - evaluate pain severity and duration, and determine the necessary duration of analgesic treatment. A key goal is to develop assessment too ls for use in research facilities by non-specialist staff. The results of the project will allow us to validate behaviour measures that can be applied routinely. We will also be able to advise on analgesic requirements when behavioural measures are compromised (eg in sedated animals)?

Amount: £248,743
Funder: The Wellcome Trust
Recipient: Newcastle University

Two-component signalling in Candida albicans. 10 Nov 2008

Stress responses are intimately linked with the pathogenicity of Candida albicans, the major systemic fungal pathogen of humans. We have found that diverse environmental stress responses are dependent upon the stress-activated protein kinase (SAPK) Hog1 in C. albicans. However, little is known about how environmental signals are sensed and relayed to the Hog1 pathway. We and others demonstrated in model yeasts that two-component signalling pathways act to relay stress signals to SAPK pathways. S ignificantly, our pilot experiments in C. albicans have shown that the two-component response regulator protein Ssk1 is required for the response to a specific subset of environmental signals that also requires the Hog1 SAPK, indicating Ssk1 to be a major regulator of Hog1. We have also identified a novel two-component signalling protein Crr1 in C. albicans, and our analysis illustrates that Crr1 is important for the oxidative stress response in a mechanism independent of Hog1 activation. This t imely proposal which builds on this strong platform of data has two key goals: (i) to define the two-component signal transduction network that relays environmental signals to the Hog1 SAPK, (ii) to characterise the mechanism of action of the novel two-component protein Crr1 in mediating the oxidative stress response.

Amount: £190,148
Funder: The Wellcome Trust
Recipient: Newcastle University

A new class of genes containing small Open Reading Frames: cellular and molecular function of the encoded peptides. 06 Apr 2009

We have characterised a non-canonical gene, tarsal-less (tal). Tal is polycistronic and only contains small Open Reading Frames (smORFs) producing peptides as small as 11 amino-acids. These peptides function as a cell signal controlling gene expression and actin-mediated cell shape changes. I plan to ascertain the mechanisms for diffusion of these peptides and transmission of their signal by: A1) Investigating the mechanism of tal uptake in a cell culture assay; A2) Organising the proteins t hat bind tal (identified candidates and new ones to be searched for) in a pathway for the transmission of the signal; A3) Clarify the mechanism for tal-dependent transcriptional control; A3) Finding out how tal affects actin cytoskeleton. I also plan to search for more genes containing only smORFs in flies and other species, and to characterise a sample that will prove their existence as a class, and their general features, by: B1) searching for homologues of tal in distant species B2) characterising putative smORF genes we have already identified, to corroborate that their function is mediated by the small peptides they encode, and to obtain further information on their general structure and sequence signatures B3) searching for further smORF genes in flies, and finally in vertebrates

Amount: £1,600,995
Funder: The Wellcome Trust
Recipient: University of Sussex

Approaches to Ancient Medicine 2009 to be held at Newcastle University on 24-25th August 29 May 2009

The purpose of the Approaches to Ancient Medicine meetings is to provide a multi-disciplinary international forum for scholarly exchange in the ever growing field of ancient medicine. The 2009 meeting is part of the very successful series of meetings that was initiated in Newcastle in 2000 (with Wellcome Trust support) and continued on an annual/biennial basis in co-operation with Reading (Prof. Helen King).

Amount: £1,500
Funder: The Wellcome Trust
Recipient: Newcastle University

Interdisciplinary Training Programme in Translational Medicine and Therapeutics at the University of Newcastle. 08 Jun 2009

Chronic cholestatic liver diseases are characterised by injury to cholangiocytes leading to progressive loss of function, fibrosis and, in their end stage, require liver transplantation. The origin of myofibroblasts in these disorders has remained controversial, what is not controversial is that TGF-? plays a key role in the development and maintenance of fibrosis. In particular, this cytokine may induce phenotypic transition of cholangiocytes into fibroblasts. Building on recent research within our group, we propose that the technique of cell lineage tracing using mitochondrial genetic mutations be applied to samples from human cirrhotic liver. By cross referencing mutations within the available cell types the exact origin of myofibroblasts can be delineated. It is known that cholangiocytes undergo oxidative stress as a component of cholestatic liver disease. Under these conditions cholangiocytes can become senescent with acquisition of p21WAF1/cip1 and the potential to acquire a pro-fibrogenic secretory phenotype. Bile duct ligation induces a ductular reaction followed by portal fibrosis. This lesion will be induced in mice and, alongside cell culture methods, allow the determination of the lifecycle of cholangiocytes during cholestatic liver disease. By determination of the factors controlling cholangiocyte cell fate it will then be possible to target specific pathways to alter or abrogate the progression of fibrosis. We hypothesise that regulation of senescence by autophagy can be altered by the application of the mTOR inhibitor XL765.

Amount: £47,818
Funder: The Wellcome Trust
Recipient: Newcastle University

Student elective for Timothy Hardy. 18 Apr 2007

Toll like Receptor-4 involvement in Airway Epithelial Wound Repair It is important to understand the regulatory mechanisms involved in airway epithelial mucosal repair, if we are to develop new therapeutic strategies to halt the progression of asthma when the disease first manifests itself in childhood. This project is premised on the hypothesis that dysregulated repair underpins the development of airway remodelling in asthma. More specifically, we propose that TLR-4 plays the key role in driving inflammation as part of the airway epithelial repair response to injury which is dysregulated in patients with inflammatory respiratory diseases, such as asthma.

Amount: £1,600
Funder: The Wellcome Trust
Recipient: Newcastle University

The Newcastle Clinical Ageing Research Unit (CARU): a new facility for integrative and translational research on early assessment and treatment for older people. 11 May 2006

We will establish an innovative Clinical Ageing Research Unit (CARU) as part of the Newcastle Campus for Ageing and Health (CAH), which will focus on developing early assessment and intervention strategies targeted at age-associated degenerative conditions. Research on ageing and age-associated disease is a Department of Health priority. Newcastle is one of the world's leading centres for ageing research with our researchers attracting over £38m in awards over the last 8 years and more than £12.5m in the last year. CARU will be intimately linked with cutting-edge research on underpinning mechanisms of ageing, including physical and functional links with the newly constructed Magnetic Resonance Centre that comprises a world class MR physics team and is being directed by a clinician with wide experience of MR research. This will optimise focus on clinical research whilst harnessing cutting edge development of MR techniques. CARU will provide exceptional opportunities for translational studies. Demographic trends mean that age-related health problems command increasing clinical attention. For the majority of these health problems, age itself is the single biggest risk factor. It is therefore of key importance to understand why the aged cell or organ becomes more vulnerable to pathology and what can be done to intervene at early stages before the less tractable end-stage pathology has developed. CARU is needed to provide the necessary specialist clinical research infrastructure for the expanding major research hub of the Institute for Ageing and Health (IAH) at Newcastle General Hospital, including extensive research on dementia and brain ageing. The CAH already includes the Henry Wellcome Laboratory for Biogerontology Research, IAH Research Laboratories (with Newcastle Brain Tissue Resource and aged animal units), and the MR Centre. CARU will support research in three of the UKCRN research networks (dementia and neurodegenerative diseases, diabetes and stroke) and have close links with the Directors of the Stroke and DeNDRoN Research Network National Coordinating Centres (Ford, McKeith).

Amount: £2,666,358
Funder: The Wellcome Trust
Recipient: Newcastle University

The Newcastle Clinical Ageing Research Unit (CARU): a new facility for integrative and translational research on early assessment and treatment for older people. 11 May 2006

We will establish an innovative Clinical Ageing Research Unit (CARU) as part of the Newcastle Campus for Ageing and Health (CAH), which will focus on developing early assessment and intervention strategies targeted at age-associated degenerative conditions. Research on ageing and age-associated disease is a Department of Health priority. Newcastle is one of the world's leading centres for ageing research with our researchers attracting over £38m in awards over the last 8 years and more than £12.5m in the last year. CARU will be intimately linked with cutting-edge research on underpinning mechanisms of ageing, including physical and functional links with the newly constructed Magnetic Resonance Centre that comprises a world class MR physics team and is being directed by a clinician with wide experience of MR research. This will optimise focus on clinical research whilst harnessing cutting edge development of MR techniques. CARU will provide exceptional opportunities for translational studies. Demographic trends mean that age-related health problems command increasing clinical attention. For the majority of these health problems, age itself is the single biggest risk factor. It is therefore of key importance to understand why the aged cell or organ becomes more vulnerable to pathology and what can be done to intervene at early stages before the less tractable end-stage pathology has developed. CARU is needed to provide the necessary specialist clinical research infrastructure for the expanding major research hub of the Institute for Ageing and Health (IAH) at Newcastle General Hospital, including extensive research on dementia and brain ageing. The CAH already includes the Henry Wellcome Laboratory for Biogerontology Research, IAH Research Laboratories (with Newcastle Brain Tissue Resource and aged animal units), and the MR Centre. CARU will support research in three of the UKCRN research networks (dementia and neurodegenerative diseases, diabetes and stroke) and have close links with the Directors of the Stroke and DeNDRoN Research Network National Coordinating Centres (Ford, McKeith).

Amount: £652,493
Funder: The Wellcome Trust
Recipient: Newcastle University

The role of mitochondria in the dysfunction of oligodendrocyte lineage cells: implications for the pathogenesis of multiple sclerosis. 06 Dec 2005

Objectives: To investigate the role of mitochondria in the dysfunction of oligodendrocyte lineage cells in multiple sclerosis (MS), I will determine the(1) presence of mitochondrial dysfunction at biochemical, protein and genetic levels in oligodendrocyte lineage cells in acute (pattern II and III), active and chronic MS lesions. (2) neuropathological features of inherited mitochondrial disorders with primary demyelination. (3) effects of mitochondrial DNA (mtDNA) abnormalities on the development, function and survival of oligodendrocyte lineage cells in vitro (MO3, HOG, Ntera2 and mouseES cells).Design: (1) Histochemistry and immunohistochemistry will be performed on post-mortem brain tissue from MS and mitochondrial disorders. (2)Molecular biology techniques (laser micro-dissection, real-time PCR and mtDNA sequencing) on dissected oligodendrocyte lineage cells from frozen MS tissue will be used to identify evidence of damaged mtDNA. (3) transmitochondrial hybrids containing inherited abnormal mtDNA and cell lines containing acquiredabnormal mtDNA (IFN-gamma and TNF induced) will be used in vitro to assess migration, proliferation, differentiation, myelination and survival using time-lapse microscopy, proliferation markers, electron microscopy for ultrastructure, immunocytochemistry for myelin proteins and apoptosis using flow cytometry.

Amount: £515,503
Funder: The Wellcome Trust
Recipient: Newcastle University

Open Access Awards. 16 Sep 2008

Not available

Amount: £30,000
Funder: The Wellcome Trust
Recipient: Newcastle University

Solid-state electrode arrays for multiple intracellular recording. 29 Aug 2008

1) To construct a solid-state alternative to conventional glass micropipettes for intracellular recording of transmembrane potentials in neurons during network activity. 2) To implant multiple solid-state electrodes in an array suitable for multi-channel parallel intracellular recordings.

Amount: £142,938
Funder: The Wellcome Trust
Recipient: Newcastle University

The role of hepatic myofibroblasts in liver injury and regeneration. 22 Apr 2008

This project will use a human recombinant single chain antibody to target hepatic myofibroblasts (HMs) in vivo. The antibody will be conjugated to gliotoxin, a compound that stimulates the apoptosis of HM. Unpublished data demonstrate that the antibody-conjugate specifically stimulates the apoptosis of HMs in vivo in animals with liver fibrosis. This project will: 1) Determine the effects of HM depletion on inflammatory, wound-healing and regenerative responses to acute liver injuries. 2) Determine whether HM depletion affects compensatory hepatocyte regeneration. 3) Determine whether HM depletion will promote reversal of fibrosis and permit regeneration of hepatocytes in the context of fibrosis and sustained liver injury.

Amount: £264,114
Funder: The Wellcome Trust
Recipient: Newcastle University