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Results

Institutional Strategic Support Fund 07 Sep 2016

Not available

Amount: £300,000
Funder: The Wellcome Trust
Recipient: University of Nottingham

A social science, mixed methods, mental health research Masters 03 Jul 2016

My research Masters will focus on mental health, developing into my dissertation, which will investigate young women and mental health in the media. In core modules, I will have the opportunity to create my own health-focused research questions. The interdisciplinary Masters incorporates modules from Health Sciences and Sociology. These include ‘Mixed methods in health research’ which focuses on philosophical and practical foundations, ‘Evaluating interventions, Services and Health and Social Care’ which will allow me to identify and demonstrate the benefit of interventions to individual users, organisations or whole populations.’ ‘Social epidemiology: theories and methods for understanding the social determinants of health’ involves exploring methods and measurements, causation and controversies, social class and deprivation, and statistical analysis. The goals of my research are to locate individuals with mental health conditions at the fore of inquiry and to generate ideas to pursue changes that improve mental health for individuals and society. I would aim to advance understanding in mental health, an area of critical need. The goal of the dissertation is to conduct research in how to improve mental health media and remove negative stereotypes, which are a barrier for people to access services and support.

Amount: £21,569
Funder: The Wellcome Trust
Recipient: University of Nottingham

Open access block grant 2016/17 30 Sep 2016

Not available

Amount: £12,183
Funder: The Wellcome Trust
Recipient: University of Nottingham

Production of a bivalent monoclonal antibody as a potent new immunotherapy for pancreatic cancer 13 Jan 2016

Pancreatic cancer is the 12th most common cancer in the world and is almost always fatal. More recently immunotherapy (stimulation of the patient’s immune response to recognised and kill their own cancer) has shown show great promise in other cancers. This makes identification of new targets and approaches for pancreatic cancer very important. Many different sugars are attached to proteins and lipids to enhance their function but in cancer they are significantly altered making them specific targets for immunotherapy. Prof Durrant and her group at the University of Nottingham have developed monoclonal antibodies (mAbs: protein drugs) that specifically target the sugars expressed on pancreatic cancers. These mAbs can directly kill cancer cells and can also stimulate the patient’s own immune response to prevent the cancer from coming back. Although, our sugars are excellent targets as they have high expression on cancers and extremely low expression on a very limited number of normal tissues, the normal expression can still lead to side effects. To reduce these side effects, without compromising efficacy, we will combine two mAbs allowing us to target two different sugars expressed on cancers but not on normal cells. This should lead to a new therapy for pancreatic cancer.

Amount: £100,757
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

University of Nottingham and University of Birmingham - Antimicrobials and Antimicrobial Resistance 30 Sep 2016

University of Nottingham and University of Birmingham - Antimicrobials and Antimicrobial Resistance

Amount: £118,573
Funder: The Wellcome Trust
Recipient: University of Nottingham

Imaging Flow Cytometry 05 Jul 2018

We seek funding for an ImageStream X Mark II Imaging Flow Cytometer to be hosted by the University of Nottingham (UoN) Flow Cytometry Facility. This exciting technology combines the speed, statistical robustness and multi-parametric data of conventional flow cytometry with the detailed localisation information of microscopy. The machine has been specified following a trial demonstration and in consultation with our extensive user group and co-applicants. It includes five lasers, high magnification, extended depth of field and automated sampler options that would make it one of the most capable machines in its class in the UK. An imaging cytometer would significantly enhance research capability by offering unique high number and high content experiments. Novel applications include the ability to detect, enumerate and characterise rare cells; the ability to dissect cell signalling events through precise measurements of nuclear translocation events or co-localisation; the study of extracellular vesicles in both eukaryotic and prokaryotic systems; precise quantification of drug delivery/internalisation; and the study of cell death mechanisms. We have established mechanisms for access, charging and an extensive client list that have indicated keen interest in this technology, and have secured a 30% financial contribution from the University demonstrating the strategic importance of this equipment.

Amount: £335,298
Funder: The Wellcome Trust
Recipient: University of Nottingham

In vitro cross-species membrane insertion of Neisserial Nalp by Campylobacter jejuni-BamA 01 Apr 2016

Outer membrane proteins (OMPs) play a fundamental role in physiological functions, multidrug resistance and virulence in Gram-negative bacteria making them essential for cell viability in a number of pathogens. Biogenesis of such beta-barrel proteins is facilitated by BamA, the main hub of the Barrel Assembly Machinery (BAM) complex. While structural characterisation of the MAS complex is yielding first results on the E. coli system (Backelar et al 2016), mechanistic details remain notoriously difficult to obtain. We propose to investigate the role of BamA from Campylobacter jejuni, an important pathogen and food spoilage organism, as a facilitator of membrane insertion of an autotransporter translocator domain from Neisseria meningitidis, NalP. NalP is a beta-barrel, which can insert at low levels spontaneously into lipid membranes in a membrane composition-dependent way. We propose to use our homology model of C. jejuni, annealed by molecular dynamics simulations (MD), to perform in silico CHARMM docking of NalP. We will investigate experimentally the degree of NalP insertion into model lipid membranes without (liposomes) or with BamA (proteoliposomes). We will use gradient separation and SDS-PAGE to quantify insertion, as well as solid state and DNP NMR to confirm insertion and to investigate specific interactions.

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

Blood vessel activation in inflamatory arthritis 01 Apr 2016

In inflammatory arthritis, articular blood vessels become activated and mediate trans-endothelial migration (transmigration) of blood borne immune cells into the affected synovium and joint space1. Immune cell transmigration also occurs in dorsal root ganglia (DRG) in a model of inflammatory arthritis and these cells contribute to the development of pain2. We hypothesise that blocking blood vessel activation, thereby preventing immune cell infiltration into the DRG, will inhibit the development of pain in inflammatory arthritis. The Student will undertake histological work to investigate the degree of immune cell DRG transmigration in arthritic animals treated with compounds to inhibit endothelial activation and immune cell transmigration. 1. Kinne RW, Stuhlmuller B, Burmester GR. Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res Ther 2007;9(6):224 2. Segond von Banchet G, Boettger MK, Fischer N, Gajda M, Brauer R, Schaible HG. Experimental arthritis causes tumor necrosis factor-alpha-dependent infiltration of macrophages into rat dorsal root ganglia which correlates with pain-related behavior. Pain 2009;145(1-2):151-9

Amount: £2,000
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

Establishment and characterisation of metastatic breast cancer cells expressing fluorescent biomarkers. 01 Apr 2016

Metastasis is the primary cause of cancer deaths. Once cancer cells have disseminated from their original location and formed "secondaries", the only therapeutic option is chemotherapy, which is toxic, ineffective and merely extends patient survival. The prognosis of patients who present with "triple negative breast cancer" (TNBC), which lack the three most common receptors targeted in BC therapy (HER2, progesterone and oestrogen), is extremely poor. TNBC cells disseminate aggressively, typically colonising lymph nodes, lungs, bones, and liver. To better understand this lethal process we are engineering a 3D bioreactor to grow TNBC cells in a relatively "native" state, and will image metastasis live in this system using fluorescence sheet microscopy. To maximise information obtained from our system we need to develop TNBC-sublines expressing fluorescently-labelled marker proteins. Certain structures are indicative of particular behaviours, and can be identified by the presence of specific proteins. Here we will use vinculin to visualise focal adhesions (FA) and assess substrate adhesion; cortactin to identify invadopodia- specialised FAs that invade new tissue; and utrophin as an F-actin surrogate, the principle cytoskeletal component that facilitates cell locomotion. The goal of this project is to generate MDA-MB-23 lines stably expressing mcherry and/or GFP-labelled vinculin, cortactin and utrophin.

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

Targeting Cholangiocarcinoma with drugs that regulate epigenetic mechanisms of tumour survival 27 Apr 2017

Cholangiocarcinoma (CCA), a malignant transformation of cholangiocytes, the epithelial cells lining the biliary tract. CCA has a poor prognosis with a high mortality rate as a consequence of a poor understanding of the molecular biology of the cholangiocyte transformation, and a consequent lack of effective drug therapies. CCA progresses with unspecific, invasive and silent symptoms, and is usually diagnosed in the advanced stages. Surgery represents the only curative treatment for CCA and has a high rate of recurrence. Chemotherapy and radiation therapies have been used in an attempt to control this cancer and improve the survival of patients with advanced CCA. However, these therapeutic strategies are not effective in prolonging long-term survival. Inhibiting epigenetic regulation of gene expression has gained momentum as a method of targetting tumours as it can inhibit the expression of multiple oncogenes and repression of multiple tumour suppressor genes at once. Epigenetic inhibitors are in several stages of clinical trails for other cancers however the study of epigenetics in cholangiocarcinoma is limited. The hypothesis of the study is epigenetic inhibitors that are effective at targeting other solid tumours will induce apoptosis and growth arrest, and reduce the expression of oncogenes in cholangiocarcinomas.

Amount: £0
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

Coupled oscillator neural networks 27 Apr 2017

The brain and its substructures can be viewed as complex networks of interacting neurons or brain centres. Understanding how the dynamics of such networks of oscillating units is affected by differences in local dynamics and network structure is important when characterising the possible mechanisms for the breakdown in functional connectivity responsible for brain diseases such as epilepsy. The proposed research will evaluate the relative importance of the roles of local neuron dynamics and network structural connectivity in determining the range of possible dynamical behaviours (e.g. global synchronisation, asynchrony, cluster states, chimera states etc) which a neural network can display and the bifurcations which occur between different network states. Using methods of phase reduction for single neuron models such as gap-junction coupled Morris Lecar neurons (near a homoclinic bifurcation) and piecewise linear caricatures of neuron models we will build (symmetric) networks of neural oscillators. The dynamical behaviours of these networks will be studied both analytically and numerically to identify which behaviours are stable, where transitions occur and the nature of these transitions. We will consider a variety of network structures including networks with symmetry where techniques from computational group theory can be employed to predict a range of possible cluster states.

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

Open access award 2011/12. 20 Sep 2011

Not available

Amount: £45,000
Funder: The Wellcome Trust
Recipient: University of Nottingham

Combination therapy of quorum sensing inhibitors and biofilm blockers for the treatment of Pseudomonas aeruginosa infection in those with cystic fibrosis. 15 Jul 2010

We shall test the hypothesis that a combination approach to quorum sensing inhibition of Pseudomonas aeruginosa (PA)will provide a new therapeutic strategy for the treatment of lung infection in Cystic Fibrosis. PA uses semi-hierarchical QS pathways to maximise its virulence and defence through AHL and AQ signal mediated co-ordinated behaviour. Garlic can block the AHL-mediated QS regulon. To increase the completeness of QS inhibition we propose to also inhibit QS at the AQ level and block t he effect of a QS regulated product, lectins. Individually garlic, AQ precursor analogues and lectin inhibitors may all interfere with QS pathways at different points. The objectives are: 1) To investigate the effect of combinations of quorum sensing inhibitors (garlic, anthranilate derivatives) and lectin inhibitors (sugars and related dendrimers) upon P. aeruginosa biofilm formation and it s susceptibility to antibiotics. 2) To investigate the impact combinations of these inhibitors have on the biology of P. aeruginosa at the transcriptomic level. 3) To investigate the conservation of this effect on single and mixed biofilms of clinical P. aeruginosa cystic fibrosis isolates. . 4) To investigate the effect of these combined treatments on the virulence of P. aeruginosa in an insect larval infection model.

Amount: £139,298
Funder: The Wellcome Trust
Recipient: University of Nottingham

The market for healers and the ethics of biomedicine in Burkina Faso. 27 Jan 2012

There has been considerable normative debate about the applicability of international bioethical thinking to medical practice and research in developing countries. Little is known about how this plays out empirically, particularly about the interaction between indigenous and international bioethical thinking. It is also acknowledged that international writing on bioethics has tended to be dominated by Anglophone values and models of research and medical practice, whose universality is contested. This empirical study of the ethics of medical practice in Burkina Faso will: describe how practitioners deal with the potentially competing claims of local and international ethical expectations; examine the influence of a francophone context and its different traditions of ethical analysis. WP1 A literature review covering international bioethics, the sociology of the professions and the anthropological study of indigenous healers; archival work on the institutional foundations of European medicine in Burkina Faso. WP2 The role of international organizations and NGOs in shaping the contemporary organisation of health services in Burkina Faso, particularly the ethical expectations embedded within their interaction with the state. The approach of regulators. WP3 The bioethics of indigenous practice and the standards adopted by local healers in interaction with consumers. WP4 The European-style medical practitioners and the ethical standards that they adopt in interactions with their consumers and their regulators. WPS PhD thesis and journal articles in French and English, together with an accessible web summary of the main findings. WP1 & WP5 will be mainly completed in Nottingham; WP2-4 will be completed in Burkina Faso.

Amount: £15,991
Funder: The Wellcome Trust
Recipient: University of Nottingham

Biomedical Vacation Scholarship 14 Jun 2010

Not available

Amount: £14,040
Funder: The Wellcome Trust
Recipient: University of Nottingham

Genome-wide association screen for susceptibility genes for pre-eclampsia in UK women. 01 Apr 2009

We propose, in collaboration with the WTCCC, to undertake GWA screening of 2225 UK women with a history of pre-eclampsia. This is the first such study of UK women, and will make use of the unique UK Genetics of Pre-eclampsia (GOPEC) DNA resource, which we believe is one of the best-characterised resources in the world for genetic studies of pre-eclampsia. Extensive phenotypic data were collected from affected women at the time of diagnosis, supervised by a clinical jury of experienced obstetrici ans with a track record in pre-eclampsia research. To increase the power for gene discovery this resource has been augmented by further samples collected by our collaborators using identical inclusion criteria. This minimises phenotypic heterogeneity, whilst ensuring that high quality data are available for the examination of phenotypic subgroups in future. Through our links with international groups actively researching the genetic basis of pre-eclampsia we propose to undertake replication and confirmation studies in a total of 2500 case and 2500 control samples from Northern European women from Norway and Finland. The aim of this research is to elucidate biological pathways underlying pre-eclampsia in order to identify novel targets for its prevention and treatment

Amount: £118,715
Funder: The Wellcome Trust
Recipient: University of Nottingham

Biomedical Vacation Scholarship 23 Jun 2014

Not available

Amount: £28,000
Funder: The Wellcome Trust
Recipient: University of Nottingham