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Results

A Multi-Site Study of Socially Engaged Art in Public Health Research within Low Income Settings. 02 May 2013

There is increasing pressure for those working in community-based biomedical research to engage more with outside communities. This is justified by statements around democratising science and supporting two-way dialogue. Still, the underlying beliefs and assumptions driving engagement in practice are rarely explored and are not always understood by those involved, and the impacts of these activities are not always captured. Socially engaged art (SEA) may provide a unique space in which genuine e ngagement can take place. The aim of this research is to identify the impact and potential of SEA as a tool for community engagement (CE), allowing for open dialogue and addressing power imbalances between researchers and communities. This aim will be addressed by using two/three in-depth studies of SEA practice within the context of biomedical community-based research across different social, cultural and political contexts. Ethnographic and participatory methods will be used to explore the behaviours and attitudes of researchers, artists and other participants in the process and how these interact. As well as exploring the creative process the research will investigate the reactions and interpretations of the outputs of these works on local audiences. Outputs will hold relevance to research governance, research programmes, funders, NGOs and engagement practitioners.

Amount: £94,364
Funder: The Wellcome Trust
Recipient: University of Sussex

Randomised controlled trial of podoconiosis treatment in northern Ethiopia 06 Jun 2012

The overall research objective of this project is to test the effectiveness of lymphoedema management in podoconiosispatients. At present, treatment of podoconiosis lymphoedema is not routinely provided by government services anywhere inthe world. In Ethiopia, where 1 million patients are estimated to live, non-government groups have developed simple,locally-appropriate treatment based on foot hygiene, emollients, bandaging, exercises to improve lymph drainage, and useof socks and shoes. Although one small proof-of-concept study suggests effectiveness of this treatment in relation toimprovement in outcomes such as leg circumference, stage of disease and quality of life, more rigorous testing isnecessary before treatment is extended within Ethiopia and to other podoconiosis-endemic countries like Cameroon, Rwanda, Uganda and Tanzania.The more detailed objectives are -1. To test whether podoconiosis lymphoedema treatment improves clinical outcomes, including decreased frequency ofacute dermatolymphangioadenitis, reduced disease stage, reduced lower leg circumference and prevalence of interdigitalentry lesions (macerations facilitating entry to micro-organisms);2. To test whether podoconiosis lymphoedema treatment improves quality of life outcomes and perceived stigma;3. To assess whether an 'intensive' model of delivery is more effective than a 'standard' model;4. To investigate whether podoconiosis lymphoedema treatment is cost-effective and has other benefits including increasedschool attendance.This will be achieved by conducting a pragmatic, single-blind randomised controlled trial with three intervention 'arms' thatwill compare two models of podoconiosis lymphoedema management in the community with delayed treatment (as control).Nine hundred adult (aged at least 16 years) podoconiosis patients located in independent households will be randomised,300 to each arm. Twenty community project assistants will support twice-weekly treatment at community sites, and tenindependent data collectors will make monthly follow-up visits. The principal analyses will be conducted at 6 and 12 monthsof follow-up.In common with many other research projects completed by our group, the results of this trial will be rapidly disseminatedto groups positioned to act on them, including Regional and District Health Bureaux, non-government organizations andpatient associations (see Communications Plan and Impact Summary). The other vital component of this trial is thetraining and capacity building it will provide, and the objectives in these areas are -5. To develop Clinical Trials capacity in Ethiopia through training and expertise-sharing by staff of the Kilifi Clinical TrialsFacility, a group with extensive experience of clinical trials support in East Africa;6. To provide high-quality supervised post-doctoral opportunities resulting in international publications for two outstandingEthiopian researchers

Amount: £150,902
Funder: The Wellcome Trust
Recipient: University of Sussex

Expression and purification of ApolipoproteinE4 - A potential target for Alzheimer's disease therapeutics 01 Apr 2016

The purpose of my project will be to express and purify the human recombinant ApoE4 isoform as the basis for conducting subsequent structural analysis and small molecule screening in an early-stage drug discovery project. In the first instance, I will attempt to reproduce previously published data with so-called "structural correctors" that convert the morphology of the "bad" ApoE4 isoform into the more benign "good" ApoE3 isoform. More specifically my aims will be: 1. Small-scale expression tests of human ApoE4 cDNA in various standard strains of bacteria (E. coli) 2. Large-scale (2-5L) expression of ApoE4 under optimal conditions identified in Step 1. 3. Isolation and purification of ApoE4 using affinity, size and/or ion exchange chromatography and fast-protein liquid chromatography (FPLC) Stretch objectives (if all goes well) include: 4. Crystallography trials and thereafter X-ray crystallography 5. Development of an ApoE4 strucutural conformation assay using a previously-published fluorescence resonance energy transfer (FRET) assay

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

Equipment for Structural Biology in the School of Life Sciences at the University of Sussex. 14 Oct 2010

X-ray crystallography is the most powerful technique available for providing the detailed structural insights into biological macromolecules, from which their mechanism, specificity and regulation can be understood. To allow us to apply this approach to the study of proteins and complexes involved in human health and disease, we propose to establish a managed multi-user facility for macromolecular crystallisation, and for X-ray diffraction data collection and analysis. Formation of the crysta ls required for X-ray crystallography needs multimilligram quantities of the protein or complex under study. Insect cells infected with engineered baculoviruses expressing target genes of interest, are an effective system for large-scale production of high-quality proteins and complexes, including post-translational modifications that are essential to function. To exploit this effective approach we propose to establish a managed multi-user facility for large scale baculovirus/insect cell express ion of target proteins and complexes. Crystal structures provide the atomic detail from which the specificity of molecular interactions can be understood, but do not define the strength of those interactions, nor their kinetics. Ancillary quantitative biophysical approaches, such as calorimetry, spectroscopy and surface plasmon resonance, are therefore also required. To access these techniques we propose to establish a multi-user facility for protein interaction biophysics.

Amount: £462,470
Funder: The Wellcome Trust
Recipient: University of Sussex

Bacterial RNA profiling to predict tuberculosis treatment failure 15 Aug 2016

At present there is no way of accurately predicting tuberculosis (TB) treatment failure and relapse to active disease. This results in the over-treatment of many patients, who might safely stop the toxic six-month therapy earlier, and necessitates lengthy and costly clinical trials to assess new therapies, thus creating a bottleneck to progress. This innovative project will test whether the transcriptional response of TB isolated from patient sputa during the first few days of treatment will predict relapse months later. Building on the applicant’s recent study demonstrating that sputa TB mRNA signatures differ between patients and reflect clinical/microbiological measures of disease, this proof-of-concept prospective patient study will for the first time define markers of relapse. TB RNA from patient sputa will be assayed by targeted and genome-wide profiling techniques at diagnosis and at multiple timepoints after the start of drug therapy. RNA yields and gene expression signatures will be analysed to determine key methodological parameters concerning the collection and detection of sputa TB RNA and to assess applicability in the UK and Cameroon. Finally, TB mRNA signatures from relapse and successfully-treated patients will be compared using this novel discovery approach to identify biomarkers that predict relapse, transforming the management of TB.

Amount: £99,201
Funder: The Wellcome Trust
Recipient: University of Sussex

ASTRODEM: Using astrophysics to close the “diagnosis gap” for dementia in UK general practice 08 Apr 2016

Dementia is one of the greatest public health challenges of our era. Timely diagnosis allows patients to benefit from current therapies, plan for the future, and maximise their quality of life. However, there is a "diagnosis gap" in UK general practice, with less than two-thirds of expected patients receiving a dementia diagnosis. Increasing diagnosis rates is a strategic aim of the UK government and NHS. We aim to close this diagnosis gap in a novel collaboration between primary care epidemiology and astrophysics. We will use a very large set of UK general practice electronic patient records (96,000 patients; 50% with dementia) spanning up to 10 years per patient. We will use a probabilistic programming framework to apply statistical techniques to model dementia onset in this cohort, allowing for the inherent variability and duration of disease development. To achieve a clinically valuable model, these multi-dimensional data will require sophisticated analysis techniques that are not currently available in medical statistics and epidemiology, but which astrophysicists use daily. Our goal is to develop a statistical model to predict risk of dementia from patients' general practice records, which will help GPs and other NHS bodies better estimate and identify cases in UK general practice.

Amount: £94,008
Funder: The Wellcome Trust
Recipient: University of Sussex

Alpha-GABa receptor modulators for the treatment of cognitive impairment associated with Huntington’s disease 22 Oct 2015

Huntington's disease (HD) is a fatal genetic disease characterised by a movement disorder that is accompanied by a decline in cognitive function and changes in mood and behaviour. The decline in cognitive function may precede the movement disorder by a decade or more and is a very important component of the functional disability associated with HD. There is, however, no effective treatment for enhancing cognitive performance in HD. The Professor John Atack from the University of Sussex aims to identify novel drugs that can enhance cognitive performance in subjects with HD and thereby address a large unmet medical need.

Amount: £1,478,688
Funder: The Wellcome Trust
Recipient: University of Sussex

Design and development of AMPA receptor modulators with a much improved safety profile as novel drugs for treating the cognitive dysfunction associated with schizophrenia and other CNS disorders 30 Jul 2016

Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications. However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problem-solving that result in a “brain fog”. These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, “normal” life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion. Professor Simon Ward from the University of Sussex has received a Seeding Drug Discovery Award to identify and develop drug which is a selective modulator of the AMPA receptor which has the potential to provide an innovative new treatment for patients with schizophrenia. If successful the team expect to have a compound ready for clinical evaluation in just over three years time. Nerve cells (neurons) communicate with each other by releasing chemicals known as neurotransmitters that interact with proteins called receptors on adjacent neurons. Levels of the neurotransmitter glutamate, which is crucial for normal cognitive function, are altered in schizophrenia. A specific subtype of glutamate receptor, the AMPA receptor, is thought to be associated with cognition and therefore increasing AMPA receptor function should improve cognitive performance in schizophrenia and thereby addressing an unmet need and revolutionizing the functional outcome of this patient population.

Amount: £992,390
Funder: The Wellcome Trust
Recipient: University of Sussex

Institutional Strategic Support Fund 07 Sep 2016

Not available

Amount: £900,000
Funder: The Wellcome Trust
Recipient: University of Sussex

Open access block grant 2016/17 30 Sep 2016

Not available

Amount: £27,001
Funder: The Wellcome Trust
Recipient: University of Sussex

Value in People award. 18 Jul 2007

Not available

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

A textual & qualitative study of the ethical, legal & clinical implications of use of the concept by multiagency mental health teams focusing on the management of people perceived to be dangerous. 22 May 2006

The original study was designed to inform the development of public policy and law around the concept of 'treatability' of people who have Severe Personality Disorder and are perceived as dangerous, as well as being relevant to clinical practice and academic debates. Although an initial paper on the policy implications was published, the untimely death of the principal researcher meant that the rich data collected from 47 in-depth interviews with relevant professionals has been left unanalysed and not disseminated. The aim of this proposed project is to update the literature collection, perform analysis on the interview data, and to disseminate the findings to academic, policy and user groups.

Amount: £9,513
Funder: The Wellcome Trust
Recipient: University of Sussex

Veterinary science, transboundary animal diseases and markets: pathways for policy in Southern Africa. 28 Feb 2006

Key to the future of livestock production in Africa - and constraints on meeting the high hopes of a 'livestock revolution' as a spur to stagnant agricultural sector growth - are the presence of transboundary animal diseases and the consequent escalating costs of regulation and meeting export standards. Focusing on the case of foot and mouth disease (FMD) in southern Africa - and specifically Botswana, Nambia, South Africa and Zimbabwe - this research will explore the economic, social and political trade-offs arising from disease control strategies focused on promoting commercial beef exports which are premised on the ability to separate a 'disease free' commercial sector from endemic areas through strictly enforced buffer and surveillance zones, and movement control. The key question is: given limited resources and capacities and growing costs, does it make sense to persist with this status quo and ensure disease freedom? Or are there alternatives that benefit a wider group of producers, are easier to implement, yet maintain access to important export markets and so foreign exchange revenues? Four country-based teams, coordinated by IDS and supported by project advisors, will investigate the policy processes in each country: how choices are made and by whom and with what criteria, to uncover the different scientific and economic arguments, policy actors and interest positions involved. The project will then bring the different players together in a series of policy dialogue workshops to explore different future policy scenarios (and their trade-offs), through a deliberative and participatory process. The main audience for both the analysis and methodological approach will be national and regional (SADC) level policymakers working on the intersections of animal health/disease control and marketing/trade policy. The policy dialogues will engage diverse stakeholders - livestock producers, regulators, processors, exporters and scientists - with a view to encouraging dialogue across usually divided sectors and across the region.

Amount: £148,704
Funder: The Wellcome Trust
Recipient: University of Sussex

Analysis of genome maintenance pathways by live cell imaging. 25 Feb 2009

Maintaining a stable genome is a vital necessity for all cells. This is achieved by coordinating DNA replication, DNA repair and the accurate segregation of the replicated sister chromatids (or homologous chromosomes in the case of meiosis) among the daughter cells. All these processes are subjected to complex and dynamic regulation and take place in different cellular compartments at different times in the cell cycle. Accurate and extensive observation and analysis of these processes in living cells is crucial to unravel the complex mechanism of the different genome maintenance pathways and requires advances imaging technologies. This proposal comprises a variety of research projects that are primarily focused on the analysis of genome maintenance pathways using live cell imaging. We are proposing to analyze chromosome segregation during meiosis, visualize the formation and dissolution of DNA double strand break repair complexes, checkpoint proteins, centrosomes, chromosomal passenger proteins during mitosis, and vesicle trafficking in neurons. What these projects have in common is a requirement for the analysis of living cells using up to date imaging technology. A Delta Vision imaging station would therefore be of great benefit for our research on genome stability.

Amount: £191,078
Funder: The Wellcome Trust
Recipient: University of Sussex

Adoption of rapid ethical appraisal as a practical method of assessing ethical issues relating to biomedical research projects in Ethiopia. 04 Jun 2009

The proposed research will test whether Rapid Ethical Assessment can be introduced as a mainstream tool to enhance biomedical research ethics appraisal in Ethiopia. Review of literature will shape a quantitative study to assess the most important issues to have affected research ethics review todate. A qualitative study will then explore deeper sociological, anthropological and ethical dimensions to the issues surrounding ethical appraisal. From the information gathered, tools based on the Rapid Ethical Assessment used in the Gambia will be developed and presented at a one-day stakeholder workshop. After feedback from participants, the tools will be piloted in at least three community-based epidemiologic research projects in Ethiopia. Basedon evaluations made, the tools will be further refined, and presented to a wider audience through a second 3-5 day workshop. A database made up of Rapid Ethical Assessments preceding a range of studies will be compiled, and will beavailable to interested researchers, on application.

Amount: £96,939
Funder: The Wellcome Trust
Recipient: University of Sussex

The tectorial membrane and the sensory hair bundles of the inner ear: mechanisms of development and effects of deafness-related mutations. 04 Feb 2009

The aim is to understand the development, maturation and dysfunction of two key components of the cochlea, the tectorial membrane and the sensory hair bundle. Analysis of mice with mutations affecting the structure and attachment of the tectorial membrane, and misexpression of tectorial-membrane proteins, will reveal the molecular mechanisms underlying the normal development of this matrix and how its constituent elements are organised. Mouse models will be used to analyse why mutations in the g ene encoding Tecta cause progressive forms of hereditary deafness and if mutated Tecta protein exacerbates the detrimental effects of loud sounds. Ectopic expression of the hair-bundle link protein stereocilin will be used to determine if it can mediate tectorial-membrane attachment. Targeted inactivation of the enzymatic and G-protein-mediated activities of two orphan receptors of the hair bundle (Ptprq and Vlgr1) will assess structural roles for these proteins, and imaging techniques will dete rmine if they can be force-activated. A mouse model for a novel human mutation causing aminoglycoside-induced hearing loss will be created to study how the mutant hair-bundle protein enhances sensitivity to aminoglycosides. These studies will determine how the tectorial membrane and the hair bundle develop, and reveal how environmental factors interact with mutations in inner-ear proteins.

Amount: £1,268,129
Funder: The Wellcome Trust
Recipient: University of Sussex

Functional interplay between Epstein-Barr virus and the 53BP1/ATM DNA damage response pathway during viral replication. 02 Oct 2008

Epstein-Barr virus (EBV, HHV4) is a human gamma herpes virus that poses major clinical problems worldwide. Activating viral replication in EBV positive tumour cells enhances the host immune response to the virally infected cell; this can be of therapeutic value. A multifunctional viral protein, Zta, is critical for initiating viral replication. Delineating the molecular mechanisms of action of Zta and its interactions with host proteins will greatly increase our understanding of the basic mechan isms used by EBV to replicate and may suggest future avenues to modulate Zta function in therapeutic settings. EBV interacts with the DNA damage response (DDR) pathway through Zta: it interacts with the DDR protein 53BP1 directly and a Zta-associated viral protein kinase directs the phosphorylation of H2AX. Furthermore, ATM is activated during EBV replication and contributes to viral replication. Here we will identify the steps of EBV genome replication that are influenced by DDR activation, focusing on the chromatin environment around the origin of lytic replication and the generation of linear DNA genomes from the concatameric replication product. Furthermore, we will fully characterise the Zta/53BP1 complex during replication and identify the contribution of viral protein kinase to functional modulation of components of the complex.

Amount: £281,251
Funder: The Wellcome Trust
Recipient: University of Sussex

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