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Results

Determinants of effectiveness of a novel community health workers programme inimproving maternal and child health in Nigeria. 28 Oct 2014

The AIM of this project is to inform strengthening and scaling up of community health worker (CHW) programmes. This will be done by investigating two implementations (with and without conditional cash transfers) of a Nigerian CHW programme, to understand what factors, under what conditions, promote equitable access to quality services, and improve maternal and child health outcomes. We will: 1. Understand of the context and the process of implementation of the interventions; 2. Identify, assess and compare the intervention outputs and outcomes; 3. Develop a model of complex relations between the actors, context, implementation process, outputs and outcomes of the interventions; 4. Develop transferable best practices for scalability and generalizability of the interventions. This five-year study will be implemented in two States in Nigeria - Niger State in the North and Anambra State in the South, identified in consultation with the Federal MOH and SUREP national programme officer. The project is designed as a multidisciplinary and mixed methods study, using qualitative and quantitative methods. Realist evaluation will be an overall platform for the study, which will use economic evaluation, social sciences and statistical analysis. Qualitative data will be collected using in-depth interviews with facility managers, community health workers, PHC staff; facility exit interviews and focus group discussions with service users and their families. Quantitative data will include existing data from HMIS and SURE-P programme and structured facility exit survey with pregnant women. Analysis of quantitative and qualitative datasets will be integrated, to allow in-depth exploration of emerging issues and continuous triangulation of findings. Project results will be disseminated widely through development of policy briefs, presentations at management meetings, newsletters and press-releases, to ensure their uptake in policy and practice in Nigeria and wider.

Amount: £264,983
Funder: The Wellcome Trust
Recipient: University of Leeds

High performance mass spectrometry: applications for the Cambridge biological sciences community. 11 Jun 2015

A major science focus across Cambridge is the application of state-of-the-art technologies to answer fundamental questions in biology, health sciences and translational medicine. These increasingly include high resolution proteomics and analysis of rare DNA and RNA modifications. Funds are requested to assist in the purchase of an Orbitrap Fusion Tribrid Mass Spectrometer, which combines quadrupole, Orbitrap, and linear ion trap mass analysers to provide an unprecedented depth of proteomic an alysis. Unique Tribrid architecture and Dynamic Scan Management allow simultaneous precursor isolation, fragmentation, and data acquisition in both Orbitrap and ion trap mass analyzers, maximizing the through-put and amount of high-quality data acquired. Improved sensitivity, scan rate, and mass resolution significantly increase proteome coverage and enhance the ability to positively identify more low-abundance proteins, while the use of novel SPS MS3 technology provides unparalleled accuracy of protein quantitation and identification when using isobaric mass tags. Overall, the instrument will: analyse the most challenging low-abundance or high-complexity samples; identify more proteins and their modifications; quantify their levels more accurately; and increase capacity of the Cambridge Centre for Proteomics, allowing greater user access and hence enhance science research.

Amount: £489,536
Funder: The Wellcome Trust
Recipient: University of Cambridge

Modern Cryo-Electron Microscopy with Direct Electron Detection at the University of Leeds. 11 Jun 2015

Funding is requested to buy a modern, cryo-capable, electron microscope to replace an outdated instrument at the end of its useful life. Data collection is currently slow and inefficient, and we cannot achieve the resolution that modern instruments allow. The new microscope will be more stable, automated, and equipped with a direct detector of the kind that is revolutionizing EM. We will also purchase the infrastructure to handle the enormous data flows that we will generate. This will transform electron microscopy in the Astbury Centre and support a wide range of biomedical projects in areas such as infection, degeneration and cancer. For 1M of Trust funds, and University investment of 1.7M, the new microscope will enable cutting-edge biological EM, including: 1) Pushing the structure determination of biological macromolecules (and their complexes) to the highest possible resolution, which in many cases will be close to atomic resolution (3-5 ). 2) Allowing us for the first time t o solve the structures of smaller macromolecules and complexes (>200-300 KDa) 3) Determining the structures of relatively lowly populated functional states in heterogeneous and/or dynamic systems 4) Performing tomography studies of unique biological events such as the entry of a virus into its host cell.

Amount: £1,000,000
Funder: The Wellcome Trust
Recipient: University of Leeds

High resolution imaging . 11 Jun 2015

Microscopy is a fundamental tool for studying cellular processes at subcellular resolution, and for dissecting in fine detail the mechanisms by which these occur. Research at the CIMR aims to understand the cellular basis of disease, and the microscopes requested in this application will be vital for our continued study of fundamental cell biological processes, with particular emphasis on membrane trafficking, organelle function, protein homeostasis and folding, the cytoskeleton and autophagy. R esearch goals of the co-applicants highlighted here include the study of adaptor proteins in the formation of specific transport vesicles and control of cargo selection (Robinson lab); the regulation of endosome to Golgi transport (Seaman lab); the roles of myosin motors in membrane transport processes and autophagy (Buss lab); and the mechanisms driving T cell polarization during immune synapse formation and killing (Griffiths lab). The microscopy equipment requested will permit complementary essential analyses for this research, including improved quantification of phenotypes and unbiased cell screening, increased resolution for live cell imaging, improved widefield imaging over longer time periods, and analysis of ultrastructural detail in fixed samples.

Amount: £500,000
Funder: The Wellcome Trust
Recipient: University of Cambridge

Open access award 2015/16. 21 Sep 2015

Not available

Amount: £51,335
Funder: The Wellcome Trust
Recipient: University of Leeds

Open access award 2015/16. 21 Sep 2015

Not available

Amount: £500,000
Funder: The Wellcome Trust
Recipient: University of Cambridge

Development of small molecule inhibitors of Ebola virus genome replication 25 Aug 2015

Development of small molecule inhibitors of Ebola virus genome replicationThis Pathfinder project will address infection with Ebola virus (EBOV), which has a human mortality rate of over 50%. EBOV is a member of the Filoviridae family (genus Ebolavirus), a negative strand RNA virus that is highly transmissible and causes severe haemorrhagic fever. The recent outbreak of EBOV in West Africa has highlighted the lack of effective therapeutic options for the treatment of this infection. Efficacious small molecule inhibitors of the virus are therefore needed for the rapid treatment of EBOV infected individuals, but their development has been hampered by the requirement to propagate EBOV under Biological Safety Level 4 (BSL4) containment.The project team, led by Professor Mark Harris at University of Leeds, propose to use a combination of in silico drug design and a mini-genome system, which accurately and faithfully recapitulates the essential processes of EBOV gene transcription and genome replication under BSL2 conditions. The team will design small molecule inhibitors based on known high-resolution structures of EBOV proteins involved in these processes, in particular focussing on the essential nucleocapsid protein. This approach builds on existing strengths at the University of Leeds, combining an innovative approach to in silico drug design with extensive experience in both virology and structural biology. The project aims to deliver drug-like lead compounds that can be further developed into therapeutic agents.

Amount: £204,959
Funder: The Wellcome Trust
Recipient: University of Leeds

Developing a unique single approach to the prevention and treatment of geneticZ alpha-1 antitrypsin-related emphysema and liver cirrhosis 30 Apr 2015

Z antitrypsin (Z-AT, severe alpha-1 antitrypsin deficiency) is an incurable and fatal genetic disorder. The mis-folded Z-AT promotes specific intermolecular polymerisation principally in the hepatocyte leading children and adults to develop liver cirrhosis and cancer which results in significant disability and death. The intracellular aggregation results in a failure of secretion which causes progressive COPD in the third decade of life, respiratory failure and death. There is a significant unmet need as current treatments are solely palliative; with only a fortunate minority receiving organ transplantation. Our work has identified a unique approach to treatment through compounds that inhibit Z-AT polymerisation and allow secretion of functional Z-AT. We have demonstrated proof of concept in cells for a lead compound and identified a hit series with a similar cellular effect This project aims to build detailed structure activity relationships on the most promising series, and secondly we will perform profiling of early prototype compounds in PiZ transgenic mice to obtain in vivo proof of concept. This work will bring us closer to a treatment for severe alpha-1 antitrypsin deficiency.

Amount: £149,926
Funder: The Wellcome Trust
Recipient: University of Cambridge

Targeting protein kinase Ck2alpha from outside the active site 30 Apr 2015

It is estimates that half of the people born after 1960 will be affected by one or another type of cancer during their lifetime. These are complex, heterogeneous and hard to treat diseases with significant impact on the society and novel therapeutic solutions are desperately needed. Different types of cancers, due to their genetic heterogeneity, require different, specialised treatments, and many cancers have no effective therapies. We hope to contribute to the fight against cancer by targeting a ubiquitous, constitutively active protein kinase CK2a that promotes cellular survival and suppresses apoptosis. We have identified new binding sites for small molecule inhibitors in Ck2a and will exploit this finding to develop more potent inhibitors with novel mechanism of inhibition and better specificity than currently available CK2a inhibitor in clinical trials. We will use structure-guided drug design to achieve this goal, and to obtain proof-of-concept data to support future funding applications to progress these molecules towards clinical candidates.

Amount: £141,948
Funder: The Wellcome Trust
Recipient: University of Cambridge
Amount: £150,473
Funder: The Wellcome Trust
Recipient: University of Leeds
Amount: £150,473
Funder: The Wellcome Trust
Recipient: University of Leeds

Leeds, Structural Biology. 22 Jun 2015

Not available

Amount: £150,473
Funder: The Wellcome Trust
Recipient: University of Leeds
Amount: £150,473
Funder: The Wellcome Trust
Recipient: University of Leeds
Amount: £150,473
Funder: The Wellcome Trust
Recipient: University of Leeds
Amount: £164,033
Funder: The Wellcome Trust
Recipient: University of Cambridge
Amount: £164,033
Funder: The Wellcome Trust
Recipient: University of Cambridge
Amount: £164,033
Funder: The Wellcome Trust
Recipient: University of Cambridge
Amount: £164,033
Funder: The Wellcome Trust
Recipient: University of Cambridge