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Results

The Animal Research Nexus: Changing Constitutions of Science, Health and Welfare 01 Feb 2017

This five-year collaborative programme will develop approaches for understanding laboratory animal research as a nexus, asking how reconceptualising connections and generating communication across different perspectives can contribute to improving the future of animal research. New research will draw attention to historical independencies between science, health and welfare; identify challenges emerging at the interfaces of animal research and create opportunities for informing policy and public engagement. We suggest collaborative approaches are essential for understanding how rapid transformations across science and society are changing the patterns of responsibility, trust and care which hold together, or constitute, this nexus. We will deliver new: integrated research across the social sciences and humanities, using historical research to inform understanding of present challenges and create new engagement opportunities for the future; interactive research projects, co-produced with researchers, animal suppliers, veterinarians, publics and patients, to investigate the contemporary dynamics of animal research; interfaces for generating cultures of communication with publics, policy-makers and practitioners across the animal research nexus. This programme brings together five leading researchers on the social and historical dimensions of animal research, uniting the strengths of five institutions, engaging creative practitioners, and advancing the work of five early career researchers and three PhD students.

Amount: £351,802
Funder: The Wellcome Trust
Recipient: University of Nottingham

DNA-clustering in yeast 31 May 2018

We propose to describe mathematically the processes by which telomeres form clusters in the nuclei of yeast cells. It is thought that this is due to the presence of proteins which bind to the telomeres. We wish to investigate the processes which determine cluster size through: 1. forming a mathematical model of the attachment processes through which proteins bind to telomeres. This may involve a site exclusion process, whereby the protein binding rate slows due to the declining number of vacant protein binding sites as the telomere `fills up'; 2. constructing a mathematical model of the aggregation of telomere-protein complexes into clusters, and determine which rate parameters are key to controlling cluster size; 3. investigating the rate of equilibration of these processes. The models we construct will have the form of systems of coupled ordinary differential equations. Through a judicious choice of rate constants, explicit equilibrium solutions will be obtainable, allowing available data to be fitted. Numerical simulations of the process will also be performed, to verify that the equilibrium solutions are accessible within biologically realistic time periods.

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

Open access publishing costs 2014/15. 15 Sep 2014

Not available

Amount: £11,495
Funder: The Wellcome Trust
Recipient: University of Nottingham

Characterising the Anti-inflammatory Properties of Cordycepin 27 Apr 2017

Cordycepin is an extract that is purified and isolated from Cordyceps Militaris, a specific strain of caterpillar fungus. It is commonly found in traditional Chinese medicine however my research aims to determine whether the compound may also be implemented in conventional medicines for the treatment of cancers and inflammatory diseases. My supervisor has already established that cordycepin down-regulates gene expression by inhibiting the polyadenylation step involved in the formation of the mRNA transcript. However, I will be investigating the effects of cordycepin on the metabolic activity and the translocation of a particular transcription factor associated with stimulating the expression of inflammatory genes in tissue culture samples containing macrophage-like haemocytes. This will be compared to other fungal extracts of insect-infecting and non-insect infecting origin to identify whether suppression of the anti-inflammatory response is replicated across a range of these compounds. Various analytical techniques will be employed such as MTT assaying and immunohistochemistry. The end results of my study will allow me to conclude how cordycepin affects the immune response and whether certain fungal extracts can be used in new immunosuppressive drugs for the future.

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

Dopamine D1 Receptor Regulation of Contextual Fear Learning 27 Apr 2017

Post-traumatic stress disorder (PTSD) is characterized by abnormally persistent memories of fear-related stimuli, is inadequately treated with currently available therapies, and is therefore a huge societal and economic burden. Clinical and preclinical evidence implicates key brain regions, such as the hippocampus and amygdala, in the pathophysiology of PTSD and in fear learning and memory processing. During contextual fear conditioning, rodents are trained to associate an environment with receiving aversive electric shock. This entails encoding a representation of the context, which becomes associated with shock. Evidence indicates that dopamine transmission is also crucial for associative learning and we have shown that blocking dopamine D1 receptors in the hippocampus or amygdala impairs contextual fear conditioning (Heath et al., 2015). In this study we will determine the effects of systemic D1 receptor blockade on encoding the contextual representation and the context-shock association in rats by using a two-stage conditioning procedure in which these two dissociable aspects of contextual fear conditioning are encoded separately over two days of training. We will first validate the two-stage conditioning procedure. We will then examine the effects of a D1 receptor antagonist given before the first and/or second day of training, before testing memory drug-free the following day.

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

A Realist Review of Clinical Pharmacists Working in GP Surgeries 27 Apr 2017

The clinical pharmacists in GP practices pilot is a world leading initiative to improve health care delivery in England. 500 clinical pharmacists are working in general practice as part of a pilot, launched in July 2015. As part of the evaluation of the project this research will consist of a descriptive narrative synthesis and a realist review. The Major research quesion will be what works for whom in what circumstances in relation to the role of clinical pharmacists in general practice. The likely other research questions which will be identified as the research goes along will focus on the impact of training, perspectives of patients, perceptions of general practice staff, how the organisational and system factors within the general practices influence the roles played by clinical pharmacist? What factors (pharmacist, patient, practice) influence the successes and failures of clinical pharmacists in general practices? Studies of pharmacists working in general practice and similar areas additional relevant publications e.g policy documents, reports will be identified, reviewed, theorised and summarised. Gaps in the knowledge base will be identified and areas for future resreach recommended.

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

The early life immune response and pain 27 Apr 2017

Immune responses are key sensitizers of nociceptive fibers. In early life pain thresholds are lower and behavioral responses to pain are exaggerated and uncoordinated compared to adults. Inflammatory stimuli provoke a well-defined series of events in adults that result in tissue swelling and hypersensitivity of the inflammed tissue. In early life, however, these same stimuli whilst causing swelling fail to produce hypersensitivity. Recently we have been investigating the altered cellular response of neonatal, juvenile and adult Sprague-Dawley rat skin to a range of inflammatory stimuli (carrageenan, complete Freunds adjuvant (CFA)). We have collected tissue postmortem and have begun to investigate the phenotype of specific circulating and tissue resident immune cells engaged in the inflammatory response and how this changes with age. The aims of this summer studentship will be to acquire the skills to perform immunohistochemistry and TaqMan qPCR in these samples to investigate the expression of neuroactive molecules expressed in these cells at defined time points post-inflammation in each age. These will be markers of pro- and anti-inflammatory signaling molecules and cell surface expression of cell specific markers (mRNA for IL-1ß, TNFalpha, IL-10, IL-6 immunohistochemical presence of endothelin-1, neutrophil elastase, mannose receptor). Expression of these will be quantified.

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

The effect of opioid receptor drugs on astrocyte function 27 Apr 2017

Astrocytes are multifunctional cells of the central nervous system that play key roles in development, homeostasis, neuromodulation, and inflammation. In recent years, the roles played by astrocytes in the development of chronic pain have received increased scrutiny. Evidence that astrocytes can contribute to the sensitization of neuronal circuits linked to nociception has led to renewed interest in the potential of astrocytes as a therapeutic target for intervention in chronic pain. Morphine remains the most effective treatment for pain, despite decades of research into alternatives. Despite this, very little is known of the effect of opiates on astrocyte function, or even whether astrocytes in the spinal cord express functional opioid receptors. The goals of this project are to address this gap in knowledge, by testing for the expression of mu-opioid receptors in astrocytes cultured from the spinal cord. Through both direct labelling for the receptor, and by testing receptor agonists and antagonists for activity in calcium and cyclic AMP signalling pathways, we will determine whether functional receptors are present in the cells. Success in these goals will illuminate whether opiates may act in part via modulation of astrocyte function, and whether this may contribute to analgesic effects.

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

Open access award 2013/14. 16 Sep 2013

Not available

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

Modern Dwelling and the Healthy Body Culture in Germany, 1870-1933. 28 May 2013

I am planning to undertake archival research in Germany for my research project, Modern Dwelling and the Healthy Body Culture in Germany, 1870-1933. The sources and areas of inquiry include a number of disciplinary frameworks. In addition to art and architectural history, this study draws from medical histories and histories of German reform movements to set up a context for the healthy body culture and its influence on domestic architecture. The sources used are books and articles written by architects and critics, architectural drawings, photographs, furniture catalogues and popular hygienic literature including hygiene and health manuals, family advice books, advertisements featuring hygienic domestic products, illustrations of the healthy and degenerate bodies, books and articles written by physicians and life reformers. The project is not only concerned with the physical transformation, but also the changing perceptions of the dwelling.

Amount: £4,998
Funder: The Wellcome Trust
Recipient: University of Nottingham

Biomedical Vacation Scholarship 24 Jun 2013

Not available

Amount: £26,640
Funder: The Wellcome Trust
Recipient: University of Nottingham

The effectiveness of mass media campaigns in reducing smoking, second-hand smoke exposure and smoking-related disease in England and Wales. 07 Nov 2011

This research will evaluate the effectiveness and cost-effectiveness of anti-tobacco mass media campaigns in England and Wales since 2004 using key indicators of smoking behaviour and smoking-related health outcomes in the general population, and in specific population groups. We will use a combination of time series analysis and longitudinal panel study analysis, using data from national datasets. Our outcomes will include smoking prevalence, rates of smoking cessation medication prescriptions, and GP consultations for children's respiratory disease (The Health Improvement Network primary care data), NHS quitline calls, NHS stop smoking service (SSS) attendees and 4 week quitters, NRT sales, Health Survey for England children's cotinine measurements, and Hospital Episode Statistics on acute MIs. Autoregressive time series models will be used to estimate population-level change in smoking behaviours and health outcomes in response to specific campaigns, or month-to-month change in advertising reach and spend, specifying the appropriate autoregressive process and transfer function, and modelling underlying trends, seasonality, and impacts of other tobacco control policies. Longitudinal analysis will use International Tobacco Control (ITC) UK data of over 2000 adult smokers and recent ex-smokers to assess individual changes in smoking behaviour and attitudes pre and post campaigns using random effects regression models. The economic model will link mass-media campaigns (via expenditure and coverage) to intermediate stop-smoking outcomes (calls to quit helplines, SSS attendance), the impact of those stop-smoking outcomes on intermediate health outcomes (AMI and respiratory disease) and the costs avoided following reductions in those health outcomes. The study will provide evidence as to whether government spending on mass media campaigns is effective and cost-effective, and for prioritising future funding to maximise its impact and reach its target audience.

Amount: £45,496
Funder: The Wellcome Trust
Recipient: University of Nottingham

Analysing genomic data from hospital superbugs 01 Apr 2016

We will analyse patient-level data on nosocomial pathogens (e.g. MRSA) including whole-genome-sequence data. Key goals include improving our quantitative understanding of transmission and assessing the effectiveness of control measures. The analysis methods are state-of-the-art techniques involving detailed individual-level stochastic models and computationally-intensive algorithms within a Bayesian statistical framework. By estimating parameters in the models, along with the associated uncertainty attached to these estimates, we can directly address particular questions of interest.

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

Developing a novel fluorescent antagonist binding assay to probe the ligand binding sites of the human Gastrin Releasing Peptide receptor 01 Apr 2016

Fluorescent ligands are an innovative approach to the study of receptor molecular pharmacology,capable of replacing radioactive tools in studies of binding and cellular localisation of unmodifiedreceptors, and also of exploring the dynamics of ligand-receptor interaction through high resolutionimaging approaches. The purpose of this project is to characterise novel fluorescent antagonistsfor the gastrin releasing peptide (GRP) G protein coupled receptor (synthesised by University ofNottingham collaborators), a peptide messenger system implicated in gastrointestinal, immune andCNS functions such as neural processing of itch. Desi will then develop a live cell platereaderimaging assay, based on competition binding with the fluorescent ligands, to measure affinities ofrepresentative GRPR agonists and antagonists. Finally, the effects of alanine scanning mutation ina key region of the receptor implicated in ligand binding (extracellular loop 3) will be determined.These individual goals will dovetail with a wider funded international programme of work on theGRP receptor. Binding and receptor mutagenesis studies will feed into molecular modelling work byBrazilian colleagues to characterise GRP receptor antagonist binding sites, in order to betterunderstand the rationale design of these ligands as potential therapeutics for cancer, inflammationand analgesia.

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

Are dopaminergic neurons of the substantia nigra pars compacta region of the brain particularly susceptible to protein damage? 01 Apr 2016

The pathological hallmark of Parkinson’s disease (PD) is a loss of dopaminergic neurons from the substantia nigra pars compacta (SNpc) region of the brain. Why this brain region is particularly vulnerable to damage and neuronal degeneration has yet to be resolved. This project will quantify the relative protein expression of the major redox regulating enzymes: superoxide dismutase (SOD), catalase (CAT), & glutathione peroxidase (GluPx), and the protein repair enzyme, protein isoaspartyl methyltransferase (PIMT) in 7 different brain regions (pre-frontal cortex, caudate nucleus, cerebellum, hippocampus, substantia nigra pars compacta, corpus callosum, & thalamus) from Parkinson’s disease (PD) patients and age, sex, and post-mortem delay matched control subjects. Brains from a total of 10 matched PD and control subjects will be analysed. The hypothesis to test is whether the SNpc region of the brain that degenerates in PD is particularly susceptible to injury due to relatively low expression of these damage-limiting enzymes. If this study demonstrates that the SNpc has low level protein expressions, then agents aimed at reducing this selective damage, such as anti-oxidants, may have useful therapeutic benefit to combat development and/or progression of PD.

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

Open access award 2015/16. 21 Sep 2015

Not available

Amount: £11,495
Funder: The Wellcome Trust
Recipient: University of Nottingham

Salience network and coordination of brain circuits in schizophrenia. 20 Jun 2011

Structural and functional brain changes have been documented extensively in schizophrenia. Emergence of psychosis during adolescence is a well-established feature of schizophrenia. Aberrant neurodevelopment leading to disrupted coordination of brain circuits has been proposed as a putative cause. Glutamatergic dysfunction has been proposed to underlie this dysconnectivity. During normal adolescence pruning of focal brain circuits leads to the emergence of longer-range connections even in the absence of direct anatomical connectivity. A paralimbic network called Salience Network (insula and anterior cingulate) has been identified as a key circuit that matures in connectivity during adolescence. This network is thought to mediate switching between default-mode and task-active brain states by modulating the recruitment of the relevant large-scale networks, in healthy adults. Objectives: To study the nature of short-range and long-range structural and functional connectivity in sch izophrenia and to demonstrate impaired Salience Network modulation of task-related recruitment of brain circuits, using fMRI. Functional connectivity will be related to glutamate levels in insula and anterior cingulate (measured using spectroscopy). Independent Component Analysis, Graph Networks and Dynamic Causal Modeling will be employed to study functional connectivity. Tractography will be used to analyse structural connectivity. Surface-based morphometry will be employed to study struc tural covariance complementing functional connectivity.

Amount: £195,294
Funder: The Wellcome Trust
Recipient: University of Nottingham

Achieving controlled human pluripotent stem cell derivation and expansion using Inter-alpha-Inhibitor with a novel polymer substrate 19 Apr 2016

This project will combine the latest advances in synthetic surfaces with the breakthrough discovery of Inter-alpha-Inhibitor (IalphaI) as a soluble, cell attachment-inducing protein, to provide a simplified and economical culture method for human pluripotent stem cells (hPSCs). The current gold standard for hPSC maintenance in vitro still requires ill-defined components with batch-to-batch variability, such as albumin or matrigel. While these conditions have now been refined to purified recombinant components, their high cost still prohibits the large-scale expansion schemes required for therapies. Synthetic surfaces overcome this problem, they are easy and inexpensive to mass-produce, and most important, their production is flexible enough to easily accommodate variable formats depending on the project requirements. Some synthetic surfaces have already been shown to support human PSC growth and expansion, but they still require high concentrations of albumin and underperform compared to traditional methods. I aim to design a hPSC culture method combining a defined, albumin-free medium with a synthetic surface, describe its biological implications on independent hPSC lines and then translate this method to 3D microcarriers and bioreactor-based large-scale expansion. This project will pave the way to clinically safe hPSC lines and scalable culture conditions to make large-scale stem cell therapy a reality.

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

Café Connect: public engagement throughout the lifecycle of health-related research 13 Apr 2016

Our vision is to develop and evaluate an innovative model of public engagement inhealth-related research called Café Connect. Uniquely the café will engage the public in ALL stages of the research life cycle, not just dissemination. The public will be invited to contemplate, discuss and react to issues in health-related research in Nottingham Contemporary café (a relaxed, non-intimidating environment) in the heart of the community. We will run one large flagship café event aimed at the general public. Three smaller events will follow-on (quarterly) with activities focusing on specific topics - self-harm, older adult drinking and emotions in food choice behaviour. During the flagship event, focus groups will identify key issues relevant to these topics shaping project design. Focus group participants will become ‘participant-engagers’ and gather data in the next two café events supported by a project manager and ‘engagement interns’. The final event will discuss project outcomes and disseminate findings. A spoken-word event will reflect on findings from the self-harm project. Engagement experiences will be captured in responses elicited via a video booth, surveys and via observation, all synthesised by an external evaluator. The applicants are experienced in public engagement and successfully piloted the Café Connect idea in 2015.

Amount: £36,963
Funder: The Wellcome Trust
Recipient: University of Nottingham