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Volunteering Matters
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Results

Grant to Volunteering Matters 23 Mar 2015

The men go forth to Battle, the women wait and knit

Amount: £9,800
Funder: The National Lottery Heritage Fund
Recipient: Volunteering Matters
Region: North East
District: County Durham

Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 10 Mar 2009

To provide support and mentoring to people with mental health problems to help them volunteer in Newcastle.

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.

Positive Futures London 18 Nov 2015

This project, based on a established youth-led volunteering model is expanding as a result of self-referrals and is being delivered in Hackney, Haringey and Tower Hamlets. It will support young people aged 13 to 25 to deliver volunteering and social action projects which they have identified to be of benefit to the local community. The aim of project is that all of the young people who are participating in it will develop key skills and have positive experiences that will shape their personal development.

Amount: £387,576
Funder: The Big Lottery Fund
Recipient: Volunteering Matters
Region: London
District: Hackney London Boro

The analysis of structural and affinity data of the pentameric ligand gated ion channels Glycine and Histamine in a drug discovery directed approach 30 Sep 2018

The research focuses on protein gates in the brain that either inhibit or allow electrical signals to be passed on. To open these gates a specific molecule has to interact with the locking mechanism to unlock the gate and allow particles to flow through. These particles can be positively or negatively charged and depending on this charge can allow or inhibit the signal, respectively. Different gates exist to regulate the different processes these signals are activating. For example, one gate is known as the glycine receptor and this has roles in inflammation and chronic pain. Unlocking the glycine gate for the inflammation pathway could inhibit inflammation signals and decrease swelling. Our research is looking at how these gates are built and how different molecules interact in different ways to either keep the gate locked or to unlock it and allow the flow of particles. By understanding the structure of the gate and how molecules interact, drugs can be developed towards specific gates to relieve symptoms. As well as the glycine gate we also look at the serotonin, GABA, acetylcholine and histamine gates, all of which regulate different processes in the central nervous system.

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

Mechanisms of host detection and dynamic adaptation in Phytophthora capsici 30 Sep 2018

The plant pathogen Phytophthora capsici, cousin to Phytophthora infestans, the notorious instigator of the Irish potato famine, can infect a broad range of plants including peppers, tomato, cucumber and beans. One of the outstanding questions is why broad host range pathogens such as P. capsici, are able to infect seemingly dissimilar plant species with unique immune responses. One hypothesis is that upon infection of a given plant, P. capsici controls the expression of its gene catalogue, allowing on the spot adaptation to the host. We have evidence that P. capsici can turn on and off infection associated genes in response to specific host plants. This implies the presence of mechanisms that allow P. capsici to sense its host and as a consequence modulate its gene expression. To identify and unravel the mechanics underpinning this adaptability we will (i) Assess the P. capsici gene collection expressed upon infection of cucumber and pepper (ii) identify and implicate regulatory elements in adaption to host and (iii) unravel the signalling events that underpins host perception.

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

Symmetry breaking mechanisms in Drosophila neural stem cells 18 Oct 2017

The control of cell division orientation impacts on the position and function of cells. Here we focus on the genetic and mechanical control that establishes the orientation of polarity and division in stem cells. Using neural stem cells, called neuroblasts, of the developing Drosophila brain, we aim to understand how stem cells remain within niche signalling range when actively proliferating. We hypothesised that the outcome of neuroblast division provides a polarity landmark for division orientation in the next cell cycle. Consistently, we found that a neuroblast daughter cell derived signal influences Par polarity module localisation when neuroblasts divide again. We now want to identify the genes behind this symmetry-breaking event. Our results suggest that midbody-organised structures link symmetry-breaking to cortical tension anisotropies and want to test if deforming the cortex using optical tweezer microscopy can bias the orientation of Par polarity. Downstream of Par complex localisation, aPKC coordinates polarity. To dissect the pleiotropic effects of aPKC, we have generated ATP analog sensitised alleles, which are homozygous viable and can be specifically inhibited. This enables us for the first time to dissect the functions of aPKC in a temporally resolved manner that establish asymmetric cell fate localisation and cell size asymmetry.

Amount: £583,165
Funder: The Wellcome Trust
Recipient: University of Dundee

Centre for Neglected Tropical Diseases Drug Discovery 30 Oct 2016

The vision for the Centre is to help tackle the urgent unmet medical need and lack of drug discovery research for Neglected Tropical Diseases (NTDs) by creating the hub for NTD drug discovery and being the collaborator of choice for academics, Pharma and Product Development Partnerships (PDPs) in the translation of discovery science into drug candidates. The success of this vision will be evidenced by increased integration, efficiency and effectiveness of the discovery science, drug discovery and mode-of-action teams in Dundee, providing: Accelerated delivery of NTD drug candidates for our PDP partners, with an initial focus on visceral leishmaniasis and Chagas' disease. Improved paradigms for carrying out NTD drug discovery, including improved understanding of PKPD relationships and more predictive disease models. Improved methodology to determine drug modes of action and resistance mechanisms. Increased exploitation of novel drug targets through structure based drug discovery, involving collaborators worldwide. Training and support for international scientists in the theory and practice of NTD drug discovery. Increased public engagement and awareness of the impact of, and need for, new medicines for NTDs and a greater understanding of the nature and importance of drug discovery.

Amount: £13,611,794
Funder: The Wellcome Trust
Recipient: University of Dundee

University of Dundee - Molecular and Cellular Biology 30 Sep 2016

University of Dundee 4 Year PhD Programme - Molecular and Cellular Biology

Amount: £119,367
Funder: The Wellcome Trust
Recipient: University of Dundee

RNA-based mechanisms in VSG allelic exclusion 30 Sep 2018

Parasites like African trypanosomes cause diseases in animals and humans and depend upon the expression of a uniform cell surface coat that can switch to evade the host immune response. This is achieved by switching genes on and off in a process known as antigenic variation. Work in the Horn lab recently revealed a protein that controls this process. The current model indicates that the protein can bind to a specific DNA sequence and drive coat production. The protein can then carry a message to other similar DNA sequences to stop coat production at those sites, thereby maintaining a uniform coat. If correct, competition for the regulatory protein would result in a ‘winner-takes-all’ scenario, whereby one coat-producing gene emerges victorious (making all of the coat). Several experimental observations support our model but the details remain to be elucidated. My aim is to manipulate trypanosomes in such a way that coat production is either on or off. These trypanosomes will then be characterised using cell and molecular biology techniques.

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

An assay and tools for cell biological analysis of human neurogenesis 05 Dec 2016

An assay and tools for cell biological analysis of human neurogenesis

Amount: £173,366
Funder: The Wellcome Trust
Recipient: University of Dundee

Recycling polarity mechanisms controlling stem cell polarity in consecutive divisions in the developing Drosophila central nervous system. 13 Nov 2012

Asymmetrically dividing Drosophila neuroblasts keep the cell polarity and division axis robustly oriented over many cell cycles. How positional information is generated to repeatedly polarise theses cells in an oriented manner between different cycles is unknown. As the mRNA of key asymmetry genes is apically localised, I aim to study if localised transcripts are polarity landmarks in neuroblasts. I further aim to study the level of mRNA localisation in these stem cells with the aim to identify centrosomally localised transcripts that I suspect to carry cell fate information. Cell fate information is also transmitted by differential segregation of cortex bound determinants from neuroblasts to differentiating daughter cells. How the mitotic cortex gets spatially organised into compartments that carry determinants remains unknown. I hypothesise that lateral diffusion barriers or a specific distribution of phospholipids organise membrane asymmetries in mitosis. Asymmetries of the me mbrane can also be detected in interphase at the basal neuroblast cell pole, evident with a specific structure overlying the last-born daughter cell. I plan to test if daughter cells send signals to the stem cell contributing to stem cell polarity to understand how the orientation of stem cell polarity is maintained from one cell cycle to the next.

Amount: £950,354
Funder: The Wellcome Trust
Recipient: University of Dundee

Biomedical Vacation Scholarship 24 Jun 2013

Not available

Amount: £2,880
Funder: The Wellcome Trust
Recipient: University of Dundee

'eHealth Coordination Activities' 17 Sep 2012

The United Kingdom has some of the best health service data in the world. This is particularly true in Scotland, where a simple and far-sighted decision in the 1970's means that every person registered with a general practitioner (GP) in Scotland (population 5 million) is allocated a unique identifying number from a centrally maintained register called the Community Health Index (CHI). It is the key to linking health data to improve communication and the quality of care that the NHS delivers to patients. It is also vital for health research that aims to improve our understanding of how to run health services efficiently; how to treat patients more effectively; how the intimate links between our genetic make-up and the environment interact to cause disease, and how to test the safety and benefit of new medicines more effectively. We have a track record of doing this; for example, using routine information, researchers in Scotland showed that the introduction of the smoking ban in public places resulted in a reduction in emergency admissions for asthma in children aged 5-15 by 18% per annum; and have shown the long term safety, often using information collected over decades, of drugs for the treatment of many common diseases such as diabetes and heart disease. The aim of the Scottish eHealth Research Centre is to build upon these existing strengths, by bringing together a group of researchers across Scotland and the UK in a joined-up strategy. This includes experts in science, public health, clinical trials, the law, safety of medicines, the law, social science, geography and the environment. Our aim is to make better use of the wealth of good quality, routinely collected health data and other datasets, to answer some of the pressing questions facing 21st Century medicine. The number one priority if we are to do this is to maintain confidentiality and privacy by implementing the highest standards of security and governance to maintain public trust. Our Centre will therefore not only perform cutting edge research and train the next generation of researches and computer scientists that we will require to analyse these large datasets, but will also consult widely with the public to develop an acceptable approach to the use of electronic patient records. Our Centre aims to demonstrate enormous benefit for clinical, genetic, public health and health services research whilst deploying the highest standards of respect for confidentiality of information. Better use of routinely collected data, will result in substantial improvements in the health of the nation. The Centre will not only produce new knowledge but also increase the health and wealth of society.

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

'The Scottish eHealth Informatics Research Centre' 17 Sep 2012

The United Kingdom has some of the best health service data in the world. This is particularly true in Scotland, where a simple and far-sighted decision in the 1970's means that every person registered with a general practitioner (GP) in Scotland (population 5 million) is allocated a unique identifying number from a centrally maintained register called the Community Health Index (CHI). It is the key to linking health data to improve communication and the quality of care that the NHS delivers to patients. It is also vital for health research that aims to improve our understanding of how to run health services efficiently; how to treat patients more effectively; how the intimate links between our genetic make-up and the environment interact to cause disease, and how to test the safety and benefit of new medicines more effectively. We have a track record of doing this; for example, using routine information, researchers in Scotland showed that the introduction of the smoking ban in public places resulted in a reduction in emergency admissions for asthma in children aged 5-15 by 18% per annum; and have shown the long term safety, often using information collected over decades, of drugs for the treatment of many common diseases such as diabetes and heart disease. The aim of the Scottish eHealth Research Centre is to build upon these existing strengths, by bringing together a group of researchers across Scotland and the UK in a joined-up strategy. This includes experts in science, public health, clinical trials, the law, safety of medicines, the law, social science, geography and the environment. Our aim is to make better use of the wealth of good quality, routinely collected health data and other datasets, to answer some of the pressing questions facing 21st Century medicine. The number one priority if we are to do this is to maintain confidentiality and privacy by implementing the highest standards of security and governance to maintain public trust. Our Centre will therefore not only perform cutting edge research and train the next generation of researches and computer scientists that we will require to analyse these large datasets, but will also consult widely with the public to develop an acceptable approach to the use of electronic patient records. Our Centre aims to demonstrate enormous benefit for clinical, genetic, public health and health services research whilst deploying the highest standards of respect for confidentiality of information. Better use of routinely collected data, will result in substantial improvements in the health of the nation. The Centre will not only produce new knowledge but also increase the health and wealth of society.

Amount: £1,147,395
Funder: The Wellcome Trust
Recipient: University of Dundee

A Q-Exactive for high throughput proteomics 06 Oct 2011

My research programme is aimed at understanding how the nucleus is organised in mammalian cells, how specific subnuclear bodies are assembled and regulated and how nuclear structure is related to biological function and to human molecular disease. A major theme of the programme is to use a combination of quantitative in vivo and in vitro techniques to measure dynamic processes in the cell nucleus. To achieve these aims we will focus primarily on studying the dynamic properties of the nucleolus and the nuclear organisation and function of the pre-mRNA splicing machinery. We will also study the role of reversible protein phosphorylation in regulating both nucleolar interactions and the splicing mechanism. We will compare data derived from biochemical experiments carried out using nuclear extracts prepared from cultured cell lines with data on the movement and interactions of proteins in vivo in the same cell lines. We will use proteomic methods to analyse and quantitate the protein composition of nucleoli under different growth and metabolic conditions and we will characterise dynamic interactions in live cells by imaging Fluorescence Protein-tagged fusion proteins. In parallel, we will analyse the organisation and structure of nuclear factors in both transformed and normal human tissue, derived from patient biopsies, to maximise the opportunities for our work on the cell biology of the nucleus to enhance clinical practice.

Amount: £200,000
Funder: The Wellcome Trust
Recipient: University of Dundee

Determining the role and mechanism of action of the SUMO targeted ubiquitin ligase RNF4 in maintaining genome integrity. 15 May 2012

RNF4 is a RING containing ubiquitin E3 ligase with specificity for polySUMO chains that is required for the therapeutic effect of arsenic trioxide in treatment of Acute Promyelocytic Leukaemia. Recently we established that RNF4 is required to maintain genome stability in higher eukaryotic cells. Our aim is to define the role of RNF4 in the DNA damage response and establish the molecular mechanism employed by RNF4, to catalyse transfer of ubiquitin to substrate. Our objectives are 1) to use quan titative proteomics to identify proteins that are selected as polySUMO modified substrates of RNF4 in response to DNA damage. 2) to establish how RNF4 recruitment leads to generation of a ubiquitin modification that is recognised by effector proteins that translate the ubiquitin signal into functional outputs. Importance of modifications will be determined by mutational analysis using in vivo readouts of DNA repair efficiency. Mechanisms by which RNF4 influences repair will be established using in vitro systems that recapitulate defined steps in repair. 3) Having recently proposed a model for the RING mediated transfer of ubiquitin to substrate we will test this using structural, biophysical and biochemical approaches and provide a description of the complex between ubiquitin loaded E2 and a dimeric RING ligase poised for catalysis. Ultimately our goal is to determine the structure of the complex containing polySUMO substrate, RNF4 E3 ligase and ubiquitin loaded E2. This would be a fir st in its class structure and would shed light on catalystic mechanisms employed by this important group of RING ligases.

Amount: £1,922,744
Funder: The Wellcome Trust
Recipient: University of Dundee

Investigating the Regulation of Dopaminergic Neurons in C. elegans. 31 Aug 2012

Dopaminergic neurons control many aspects of behaviour in both humans and C. elegans. Therefore unsurprisingly, major human diseases like Parkinson's and Schizophrenia are associated with the malfunction of dopaminergic neurons. The nematode C. elegans is an established model organism to address neurobiological questions like the regulation of dopaminergic neurons. The specific degeneration of these neurons is the major hallmark of Parkinson's Disease and can be recapitulated following administration of the drug 6-Hydroxydopamine (6-OHDA) in mammals and worms (Nass et al. 2010). I used this drug assay to screen for mutants which render C. elegans more susceptible to 6-OHDA-toxicity. In result, 4 hypersensitive mutants were isolated and 3 additional mutants were found that do not properly specify dopaminergic fate. The identification of the corresponding genes and their subsequent characterisation will be the focus of my PhD. To our best knowledge, there is only one other gene known so far to protect dopaminergic neurons from degeneration (manuscript in preparation) and the mutants with defective differentiation promise to contribute to the existing literature. Hence, by characterising the function and molecular mode of action of these genes we expect to make important contributions to the understanding of dopaminergic neuron biology in health and disease.

Amount: £150,398
Funder: The Wellcome Trust
Recipient: University of Dundee

Molecular mechanisms in atopic skin. 01 Apr 2015

Atopic skin is characterized by widespread barrier dysfunction. Null mutations in the gene encoding filaggrin (FLG) represent a strong risk factor for atopic eczema, but 20 other eczema risk loci but their functional relevance is unclear. My recent transcriptome analysis indicates the importance of pathways within the extracellular space, lipid metabolism and stress response leading to skin barrier dysfunction. I propose to address outstanding questions to translate the significant investment in genetic research for clinical application. My key goals are to develop established skin organotypic c ulture models for testing eczema candidate genes and to investigate the role of structural variation within the epidermal differentiation complex. Selected candidate genes will be tested in vitro, offering a platform to separate the multiple genetic and environmental factors in this complex trait. I will use next-generation sequencing combined with conventional methodologies to test whether structural variation in additional epidermal differentiation genes affect eczema risk in both paediatric a nd adult case collections. Significant findings will be assessed using DNA collected as part of collaborators' ongoing clinical trials. These studies will improve understanding of eczema pathogenesis and start to bridge the gap between molecular genetics and clinical care.

Amount: £1,725,456
Funder: The Wellcome Trust
Recipient: University of Dundee

Institutional Strategic Support Fund FY2013/14 14 Oct 2013

Recruitment and Career Development ISSF has funded start-up packages (equipment, PhD studentships, laboratory consumables and relocation costs) for the recruitment of outstanding biomedical researchers. These new recruits work across cell and molecular biology, bacteriology, immunology, parasitology and drug discovery. The ISSF has also been used to provide bridging support for researchers experiencing short-term funding gaps. This flexible and reactive support has enabled PhD students and investigators to generate data for key publications and successful grant/fellowship applications. Enhancement of Research Infrastructure The ISSF has supported our strategy to have innovative core facilities in key research areas and to develop computational and informatics resources that underpin our WT funded research. Software developers have been appointed to develop computational and informatics resources to support the outstanding mass spectrometry-based proteomics facility [http://www.lifesci.dundee.ac.uk/cast/fingerprints-proteomics-facility] in the School of Life Sciences. Novel ways of managing, visualising and analysing ‘big data’ in the field of quantitative proteomics have been developed, in addition to a customised Laboratory Information Management System (LIMS). Translational Research A flexible Translation Medical Research Fund (TMRF) was used to link the strongest basic and clinical research across the University of Dundee (2011-2014). Funding was awarded on a competitive basis and 25 different projects have been supported including; Pump-priming projects, Strategic projects that benefitted several groups across the University and increase overall institutional competitiveness in translational research; and translational medicine (non-clinical) PhD projects. Public Engagement The ISSF supports community engagement activities targeted at the next generation of scientists to enhance a culture of curiosity, confidence and engagement with science with our communities. A key aim is to increase awareness of Life Sciences Research in schools in areas of social deprivation to promote widening of access to opportunities in science. ISSF funds support the appointment of a School Outreach Organiser (this post greatly increases the quality and scope of our work and supports public engagement activities of our WT funded researchers); school projects; city and rural Science Festivals, the Dundee Women in Science Festival; projects to translate science into public art; an interactive display at the Dundee Science Centre; a Life Sciences career paths booklet and website (through interviews, time-lines and photographs); Open Doors Days; Magnificent Microbes and Marvellous Microbes activities; Café Science; Bright Club science comedy; public talks and debates. The impact of activities is assessed by questionnaires and reflective feedback discussions with stakeholders. We plan a quarterly public survey in Dundee to capture audience knowledge of the Life Science Research and Wellcome Trust activities. This will give us a measure of whether public engagement activities are reaching the community.

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