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Results

LifeLines 20 Apr 2016

This is the expansion of a project supporting volunteers aged 50 plus to run activities for vulnerable older people to improve health and well-being. These have previously included art classes, creative writing, yoga and computer club. The group will expand across the city, recruiting more volunteers, supporting more than 800 new people and establishing a Men’s Network to encourage older men to socialise regularly. It will also extend its HealthLink scheme to help older people get to medical appointments.

Kilkeel RBL - Saving Our Community Venue 22 Oct 2015

The group is a community and voluntary based organisation providing a range of services and activities to the local community. They received a grant of £10,000 to make improvements to their venue so that it can be used for more classes and activities.

Grant to Royal British Legion Tipton Branch 19 May 2016

Remembering Tipton's World War One Heroes

Grant awarded to The Royal British Legion (Forest Hall) Branch And Club (Tyne & Wear) 20 Nov 1998

Towards improving access and facilities for disabled people at the Forest Hall Ex-Servicemen's Institute.

Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 13 Jul 2004

To provide daycare services to older people living in high rise flats in Newcastle.

The Dynamics of Cellular Pathways 12 Jul 2011

Transposable elements (TEs) are mobile DNA elements that account for substantial proportions of the genomes of most organisms. For example, TEs make up approximately 45% of the human genome. TEs have been shown to generatemutations leading to Mendelian diseases and cancers in humans. Despite their abundance and importance, the mechanisms that regulate TE insertion in eukaryotic genomes remain largely unknown. The overall aim of this project is to investigate the interplay between chromatin structure and TE insertions in eukaryotes using the model species, Drosophila melanogaster, to address several objectives: Objective 1. Decode the chromatin features that influence promoter targeting of the Drosophila melanogaster P element during artificial mutagenesis experiments. Objective 2. Identify chromatin features associated with de novo insertion sites of naturally occurring TEs using population-resequencing data. Objective 3. Investigate the chromatin properties of TE insertions in the Drosophila melanogaster reference genome. Objective 4. Develop robust software for the identification of de novo TE insertions in next generation sequencing data. This work will lead to important insights about the basic mechanisms of TE integration that can be used to interpret patterns of TE insertion in eukaryotes and potentially to harness TEs as vestors for genetic engineering or gene therapy.

Amount: £146,543
Funder: The Wellcome Trust
Recipient: University of Manchester

Taurine transport proteins in the placenta: novel targets for correcting trophoblast cell turnover in pre-eclampsia? 15 Mar 2011

Pre-eclampsia (PE) complicates 4% of pregnancies and is a leading cause of maternal and neonatal death. The origin of PE lies in the maternal response to abnormal placental development, in particular dysregulated syncytiotrophoblast cell turnover. For reasons currently unknown, maternal obesity increases the risk of PE. Inflammation and oxidative/nitrative stress, common features of both pregnancy conditions, can disrupt the syncytiotrophoblast cell turnover and modulate amino acid transport pro teins. In normal pregnancy, syncytiotrophoblast accumulates the amino acid taurine, a key intracellular antioxidant and osmoregulator that facilitates cellular turnover and protects cells against environmental damage. We hypothesise that inflammation and oxidative/nitrative stress modulate taurine uptake and efflux proteins in syncytiotrophoblast to reduce intracellular taurine which dysregulates cellular turnover, providing a link between maternal obesity and PE. We will determine (i) syncyti otrophoblast taurine concentration in PE and maternal obesity compared to normal pregnancy and relate changes in taurine uptake/efflux to markers of oxidative/nitrative stress (ii) whether inflammation and oxidative/nitrative stress disrupt syncytiotrophoblast turnover in vitro through effects on taurine transport pathways and intracellular taurine (iii) targets for restoring taurine concentration and/or taurine signalling pathways as potential future treatment strategies to rescue syncytiotroph oblast turnover and improve the outcome of these serious pregnancy complications.

Amount: £258,794
Funder: The Wellcome Trust
Recipient: University of Manchester

RNA functional profiling by gene deletion in a model organism. 09 Mar 2011

Saccharomyces cerevisiae is a key model organism for investigating biological processes. The Yeast Deletion Collection (YDC) for protein-coding genes has provided a valuable resource for researchers. While it is important to determine the role protein-coding genes play in biological processes, RNA is increasingly playing a central role in many biological processes. Unfortunately, RNA-coding genes are absent from the YDC. Therefore, it is essential to develop deletion strains of RNA-coding genes to provide a comprehensive gene deletion collection for genome-scale analysis and systematic analysis of RNA function. We propose to delete all annotated and a collection of recently identified unannotated RNA genes in yeast. High-throughput deletion will include unique molecular barcodes allowing identification of each deletion strain, parallel analysis and YDC compatibility. The RNA deletion strains will be used for RNA functional analysis and to probe, by next generation sequencing of barcod es, the contribution of RNA to growth of yeast in continuous culture with a variety of conditions and treatments. Selected essential RNA genes will also be deleted in the divergent yeast Sigma1278b to determine whether phenotype is influenced by genetic background. Finally, strains will be distributed to international repositories to provide a lasting and useful resource for researchers.

Amount: £357,914
Funder: The Wellcome Trust
Recipient: University of Manchester

A systems-based and whole cell tomography study of Type IV pilus biogenesis in Pseudomonas aeruginosa. 05 Oct 2010

This proposal aims to develop a novel approach to the study of the biogenesis of type IV pili in Pseudomonas aeruginosa (Pa). It is driven by the identification of small molecule inhibitors of the process, which will then be employed to generate a quantitative, systems-based model for pilus formation and to trap the biogenesis complex in particular structural states which can be observed in vivo by cryoelectron tomography. Inhibitor screening will be carried out by i) high throughput screening o f Pa ii) structure-based drug design, by experimental location of chemical fragments using X-ray crystallography applied to recombinant pilus biogenesis proteins, followed by seaches of chemical databases to identify suitable inhibitors. The effect of these inhibitors on pilus production and surface pilus expression will then be evaluated, the data quantified and used to construct a theoretical model for pilus biogenesis. Finally, we will link the effect of specific inhibitors to structural ch anges in vivo using cryoelectron tomography to calculate 3D reconstructions of Pa, from which we can draw inferences concerning the spatial disposition of pilus fibres and the formation of transient biogenesis complexes.

Amount: £299,592
Funder: The Wellcome Trust
Recipient: University of Manchester

'Mean, Moody and Monthly': Women, Medicine and Premenstrual Syndrome in Twentieth-Century Britain. 26 Mar 2009

This project examines how and why medical understandings and social meanings of premenstrual complaints changed in Britain in the twentieth century. Drawing on medical literature, archival sources, media portrayals and popular culture, I trace how the distinct disease concepts of premenstrual tension and premenstrual syndrome evolved and moved into popular idioms, occurred within specified professional, social, political, and cultural contexts, and in response to transformations in medical structures, health practices, and gender roles. I consider how the slippery, contested term premenstrual syndrome , and its pathologising of problematic behaviour, make it a paradigmatic case for testing the much discussed, but little researched, notion of the medicalisation of everyday life.

Amount: £145,338
Funder: The Wellcome Trust
Recipient: University of Manchester

Structural and functional studeies of angiopoietin/Tie2 signalling and a novelangiopoietin-like protein 21 Jul 2009

Detailed knowledge of protein-protein interactions is crucial for understanding protein structure and function, as well as the origin and progression of certain fatal disorders, such as amyloid diseases. Because an understanding of these interactions is often hindered by the nature of the interacting proteins or the process of interest per se, protein engineering and protein de novo design have traditionally been used to study complicated processes in a simplified manner. In these studies, the a-helical coiled-coil structural motif has frequently been used for protein engineering purposes, and its simplicity and regularity has also attracted much attention to elucidate and validate fundamental principles of protein folding by de novo protein design. We already successfully demonstrated the usefulness of the coiled-coil structural motif to address key open issues of amyloid fibril formation and angiopoietin function. Based on the coiled-coil structural motif, we recently succeeded in designing de novo a model peptide that folds into a coiled-coil conformation under ambient conditions but transforms into amyloid fibrils at elevated temperatures. The long-term goal of this proposal is to obtain an understanding of angiopoietin function and amyloid diseases at the molecular level. The specific objectives of this proposal are (a) to systematically dissect the driving forces of amyloid formation (e.g. native state stability, physiochemical properties and residual structure of a peptide/protein in its unfolded state, kinetics of fibril formation, fibril packing and stability) and evaluate their relative contribution to the process, (b) to elucidate the role of amyloid fibril packing in human disorders, (c) to define the mechanism of interaction of angiopoietins and their splice variants with the Tie2 receptor, (d) and to identify by mutageneis and X-ray crystallography the regions that are important for angiopoietin function. Biophysical, biochemical and cell biological method will be used to address these important issues.

Amount: £214,543
Funder: The Wellcome Trust
Recipient: University of Manchester

How does SOX9 regulate the pancreatic niche of beta cell differentiation?. 17 Jun 2009

Beta cell regeneration is an ambitious option for the treatment and potential cure of type 1 diabetes. Evidence to date indicates that understanding pancreas development is the best approach for beta cell regeneration strategies in adulthood. My research programme will investigate the transcription factor SOX9 as a critical regulator of beta cell differentiation. I propose that this role depends on SOX9 regulation of the extracellular matrix and extracellular signalling that surrounds the pancre atic progenitor cells to create a niche for beta cell differentiation. By characterising and investigating this niche during development, I anticipate gaining insights into the potential of adult pancreatic ductal cells to undergo beta cell regeneration. Experiments will be conducted using mouse models alongside normal human tissue to attempt to translate data as rapidly as possible into the cell-types of most relevance to patients with type 1 diabetes.

Amount: £1,411,155
Funder: The Wellcome Trust
Recipient: University of Manchester

Needles in a DNA-stack: large scale genetic association studies and the school curriculum. 06 May 2009

Current research in human genomics has great potential for involving students, yet it is not prominent in the school curriculum. We aim to redress that situation. Emerging knowledge of genetics in medicine has extended beyond the rare, such as cystic fibrosis, to include common diseases, such as cancer and heart disease. Large national genome-wide association studies are a method employed to help tease out the contribution genes make to these diseases. These studies raise many questions, some scientific, some ethical and some political, yet there is currently comparatively little opportunity for school-aged students to consider them. Needles in a DNA-stack will develop materials and CPD to enable genome-wide association studies to be incorporated into school curricula, and to allow teachers to introduce aspects of genomics into their teaching. We will achieve this through a diverse programme of interventions over a range of relevant subject areas. The project will embed contemporary research into school science and will enable teachers to enliven their teaching, drawing on large-scale genetic association research, such as The Wellcome Trust Case Control Consortium studies and biobanking. We intend to support teachers and their students: ? to explore genetic and lifestyle contributions to disease ? to consider the methodological challenges these studies present ? to examine the social and ethical challenges to society of setting up the studies ? to explore the potential impact of data arising from these studies We will further explore the effectiveness of our approach with the intention of applying it to other contexts.

Amount: £218,319
Funder: The Wellcome Trust
Recipient: University of Manchester

Open Access Awards. 16 Sep 2008

Not available

Amount: £40,000
Funder: The Wellcome Trust
Recipient: University of Manchester

Defining the mechanism of integrin receptor agonism and efficacy. 16 Sep 2008

Adhesion receptor signalling is essential for maintaining tissue structure and controlling cell migration. Conversely, dysregulation of adhesion contributes to the progression of a wide range of diseases by disrupting tissue architecture and allowing aberrant cell trafficking. To mediate these functions, adhesion receptors (principally integrins and syndecans) control dynamic interactions between extracellular matrices and the contractile cytoskeleton. In cultured cells, sites of cell-extracellular matrix contact are elaborated as focal assemblies of cytoskeletal and signalling molecules. These adhesion contacts are created, mature and dissolve as cells make and break contact with their environment. A long-standing challenge in the field is to understand how adhesion receptors convert ligand binding into the efficacious signals that regulate cell movement. By focusing on the mechanisms that determine receptor activation, the signalling events that coordinate the functions of different receptors, and the relationship between receptor activation and adhesion contact maturation, we aim to obtain a holistic understanding of adhesion signalling. We will employ fibroblast and melanoma cells model systems, and focus on the mechanisms of action of three fibronectin receptors: the a4ß1 and a5ß1 integrins, and syndecan-4. Specifically, we will: 1. Determine the structural basis of integrin priming and ligand activation by: Defining the intramolecular mechanisms of integrin activation induced by point mutations and stimulatory monoclonal antibodies. Solving the structure of different integrin activation state classes. 2. Elucidate the molecular basis of adhesion receptor cross-talk by: Defining the mechanisms of integrin/syndecan-interdependent Rho family GTPase regulation. Delineating the signalling events that determine integrin-specific modulation of the cytoskeleton. 3. Define the dynamic changes in adhesion contacts that integrate adhesion and migration by: Elucidating the linkage between integrin conformation and adhesion contact composition. Analysing the temporal segregation of cytoskeletal components during adhesion contact maturation.

Amount: £58,121
Funder: The Wellcome Trust
Recipient: University of Manchester

Equipment grant to fund the purchase of a multi-colour LSRII flow cytometer (University of Manchester, Faculty of Life Sciences, Immunology and Neuroinflammation groups). 13 Jul 2009

Our understanding of normal and disrupted biological processes is critically dependent on our ability to measure changes in cellular profiles and the expression of key molecules. A vital technique for measuring cellular and molecular changes is flow cytometry, which can be used for simultaneous analysis of many different cell types, molecules and signalling pathways within a complex biological sample. With recent advances in the technological capabilities of flow cytometers, it is now possible t o analyse up to 17 different cell/molecule populations in the same sample. This technology is increasingly essential to biologists, to enable analysis of specific cell populations identified by the expression of multiple different protein markers, and to analyse the production of multiple cytokines by these cells. The Immunology and Neuroinflammation groups at the University of Manchester consist of 8 group leaders, performing research that relies heavily on flow cytometric assays. Our groups do not have access to a high-specification multi-colour flow cytometer, which severely compromises the speed and scope of experiments that can be performed. Therefore, our proposal requests funds to purchase a multi-colour flow cytometer, to greatly benefit multiple research projects within the Immunology and Neuroinflammation groups.

Amount: £202,720
Funder: The Wellcome Trust
Recipient: University of Manchester

Next generation genome sequencer. 28 Apr 2009

The sequencing of large numbers of genomes has opened up numerous new exciting possibilities for novel avenues of research on a scale that was previously impossible to contemplate. More recent technological advances such as next generation sequencers have further accelerated our ability to ask questions about how the genome behaves and is modified. There are three major applications of this technology; genome resequencing (eg for mutation detection), RNA-Seq (for analysing global gene expressi on patterns) and ChIP-Seq (eg for identifying transcription factor binding sites). All these approaches map onto projects that are currently being pursued by researchers at the University of Manchester but which cannot currently be executed to their full potential due to the lack of this technology in house. In particular, several projects will be facilitated by ChIP-Seq and are centred on understanding how the genome is regulated by transcription factors and chromatin modifications in a dynamic manner. Genome sequencing will be used to help find the molecular causes underlying human disease and provide an evolutionary insight into the construction of gene regulatory modules. Moreover there is also a growing realisation that RNA-Seq is an essential discovery tool for interrogating gene expression changes in the cell.

Amount: £399,076
Funder: The Wellcome Trust
Recipient: University of Manchester

Darwin Festival at the Manchester Museum. 17 Jun 2009

Our project is a year-long Festival exploring the life of Charles Darwin, his ideas, their impact and their legacies on science and society. Currently, our existing plans for the Festival consist of three major exhibitions. We are nowseeking funding to deliver a comprehensive programme of accompanying public engagement and educational activities. The Festival will be a major component of the national Darwin programme, and the largest Darwin and evolution themed project in the North West. Commencing in August 2009, it will encompass the 150th anniversary of the publication of 'On the Origin of Species' and sustain Darwin 200 activities well into 2010 and the United Nation's International Year of Biodiversity. In developing our plans, we aim to complement existing initiatives, including those developed by the Wellcome Trust and the BBSRC, by creating a programme which draws upon the unique range of resources available to us as a leading university museum; a museum which owes its very design to Darwinian principlesof evolution, and which has a strong track record in public engagement. The Museum - situated in a world-class university and with some of the finest natural history collections in Britain - is the perfect place in which to explore Darwin's impact, both historically and in contemporary society. Working with a range of partners, from academics to community organisations, the Festival will explore the scientific, cultural and ethical implications ofDarwin's work and its legacies, providing opportunities for audiences from diverse backgrounds and perspectives to engage with the programme.

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

The histories of cancer policies and cancer care in the Netherlands and in England from c 1970, and their potential to inform policy debates. 11 Jun 2009

The histories of cancer policy and cancer services in the Netherlands and in England will be explored for the period from 1970 to 2009, including palliative care, and using interviews as well as written sources. My preliminary research suggested that policies on cancer care in these countries show sufficient commonalities and differences to allow for insightful comparisons; by including the rather different dynamics of palliative services, I hope to gain further insights. I will use the secondary literature to set the two national histories in a wide international context. I will explore how cancer care was changed by different kinds of demands (political, professional and directly from patients) and how the systems compared in terms of effectiveness and responsiveness. The differences made by 'policy' have to be measured against estimates of the change that would have happened anyway, and for this purpose studies across time, and across countries may be particularly rewarding. I will develop my findings to show more generally how histories can inform health care policy. The thesis will contribute to the histories of health services and cancer care; it will aim to encourage historical evaluation of policy; it will try to show both how policy makers could have learned from history, and what they might learn from good history now.

Amount: £79,922
Funder: The Wellcome Trust
Recipient: University of Manchester

Proprietary challenges in stem cell research: scientific innovation and global justice. 22 Sep 2009

This project aims to identify, evaluate and address, through concrete and actionable recommendations, the challenges raised by proprietary practices in stem cell research in a way that promotes both scientific innovation and the public good. Our specific objectives are to: 1) identify the challenges raised internationally by current proprietary structures in stem cell research; 2) develop a catalogue of practical, forward-looking recommendations (aimed atinvestigators, institutions, funders, governments) to address these micro-level challenges, classified according to ease of implementation, alignment with the idea of science as a public good, potential impact on the science, and other relevant factors; and 3) develop a roadmap to get from the near-term microlevel fixes to long-term solutions that foster the development of a process of scientific R&D that is supportive both of innovation and the public good. The Hinxton Group methodology of convening an international, interdisciplinarygroup of experts to explore and debate over the course of a three-day plenary meeting, will be augmented with an enhanced data collection and synthesis period conducted by the members of the UK/US steering committee plus a number of additional experts. This Executive Committee will develop the documents that will be used to frame plenary meeting discussions.

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