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Volunteering Matters
University of Bristol

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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

Codes within codes: How genetic variation influences disease through regional changes in methylation 30 Sep 2018

Inter-individual DNA methylation variation has been linked to a variety of traits and behaviours, such as BMI, smoking, and cancer, through epigenome-wide association studies (EWAS). However, these studies often do not incorporate gene expression and examine changes at single CpG sites. Often a regional change in methylation is required to actuate a downstream effect. I aim to produce new methods, to collapse DNA methylation data using multiple ‘omics datasets and histone marks as a guide. I will explore how collapsing DNA methylation data can be informed by gene expression, histone modifications and further regulatory information. I will use current methods to collapse DNA methylation data and develop new methods using large scale reference datasets, such as the ENCODE, Blueprint and Roadmap epigenomics projects. I will then apply these methods genome-wide and within larger datasets. I will then explore the association between regional methylation and a range of traits and explore potentially causal associations using Mendelian randomisation. These studies will give insights into the interplay between DNA methylation and other molecular traits, lay the foundations for future work collapsing DNA methylation in a biologically meaningful context, and could guide future EWAS.

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

The role of cerebellar circuitry in movement control and real-time motor learning 28 Nov 2017

The cerebellum is known to play a critical role in ongoing sensorimotor behaviour and learning of novel associations, but these processes remain poorly understood. The aim of this proposal is therefore to provide an extensive characterisation of the cellular and circuit mechanisms involved in motor control and learning in the cerebellum. We will probe cerebellar processing in head-fixed behaving animals using whisker movement as a model sensorimotor behaviour. We will measure neuronal activity using a variety of functional imaging and electrophysiological methods, combined where appropriate with opto- and pharmaco-genetic perturbation of specific circuit elements. Throughout the data-gathering process, we will work with theoreticians to generate a comprehensive network model of whisker representation in the cerebellum. Three discrete but interconnected aims will be addressed: 1) What are the organisational principles governing control of whisker movement within the cerebellar cortex? 2) What are the functional characteristics of inputs and outputs to cerebellar cortex during active whisking? 3) What are the mechanisms of real-time motor learning in the cerebellum? Together, we will provide unique quantitative information about the function of cerebellum in voluntary movement, and reveal how learning-related changes influence the neural representation of a well-controlled motor behaviour.

Amount: £1,498,083
Funder: The Wellcome Trust
Recipient: University of Bristol

Dissecting the cellular mechanisms which underpin Stickler syndrome and Osteoarthritis in a zebrafish model 30 Sep 2018

Osteoarthritis is the most common joint disease globally, with 8 million people suffering from this disease in the UK alone. Currently there is no cure for osteoarthritis: the only treatments available focus on pain relief with many causing unpleasant side effects when used for long periods of time. By understanding more about the genes which are involved in osteoarthritis onset, we may be able to identify new drug targets to prevent disease occurrence. To do this we need to know how changes to genes affect cells, hard tissue and soft tissue in the joint. This project will use zebrafish to understand how changes to genes, which are seen in patients with osteoarthritis, may alter joint development over time. It will also look at genes which cause Stickler syndrome, a very severe form of osteoarthritis with early onset, to further understand how osteoarthritic joints develop. This will help us to unpick what goes wrong throughout development to give rise to the altered joint shape seen in osteoarthritis, and will enable us to find potential therapeutic targets to improve the treatment of osteoarthritis.

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

Fighting global worming: understanding parasites using evolutionary genomics 04 Dec 2017

Roundworms (Nematoda) and flatworms (Platyhelminthes) are among the most species-rich animal groups. They include free-living animals, but also parasites with a dramatic impact. Worm infections (helminthiasis) ruin farm animals and plants, and infect more than half of the worldwide human population decreasing birth outcome, cognitive development, and school and work performance. Understanding their biology is imperative to fight these organisms with a huge socioeconomic importance. This is a pilot study to apply evolutionary genomics to the origins of parasitism and drug targets detection. Genomes compared under the light of their evolutionary relationships will define differential genetic content (gene gains and losses) between parasites and non-parasites. This will provide new insights on how harmless organisms became parasitic at genome level, but will also detect new targets to fight these diseases. Parasite-specific gains will constitute ideal drug targets, providing high specificity; gene losses will indicate deficiencies in the parasites physiology that can be also attacked. The application of evolutionary biology to discover drug targets is highly original, building on the emerging field of evolutionary medicine, and has never been applied to macroscopic parasites. This project will be the basis of future research and collaborations to further develop drugs to target these diseases.

Amount: £99,870
Funder: The Wellcome Trust
Recipient: University of Bristol

DISSECTING ACTIN-DEPENDENT CHROMOSOME COHESION IN MAMMALIAN OOCYTES 21 May 2018

When immature oocytes develop into eggs, a specialised form of cell division called meiosis segregates the chromosomes. Meiotic chromosome segregation errors are remarkably common and can give rise to aneuploidy, a leading cause of human embryo deaths and genetic disorders such as Down’s syndrome. I recently showed that accurate chromosome segregation in mammalian eggs critically relies on actin (Mogessie and Schuh, Science, 2017). I have now obtained data that suggest a previously unknown function of actin in chromosome cohesion, a mechanism that prevents untimely separation of chromosomes. It is known that loss of chromosome cohesion underlies aneuploidy in human and mouse oocytes. Actin-dependent chromosome linking is therefore a novel finding that deserves detailed investigation. Here, I will address actin-dependent cohesion in mouse oocytes by combining advanced microscopy techniques with drug-based loss-of-function assays. I will further dissect this novel mechanism by restricting loss-of-function assays to meiotic chromosomes and their kinetochores. Ultimately, I will examine whether actin can be used to bolster weakened cohesion and prevent aneuploidy in oocytes. Findings from this study will define a new ‘chromosome gluing’ mechanism that can potentially be repurposed to prevent aneuploidy in oocytes of fertility treatment patients.

Amount: £100,000
Funder: The Wellcome Trust
Recipient: University of Bristol

Synaptic dynamics underlying microcircuit plasticity in mouse barrel cortex 30 Sep 2018

Changes in the strength of connections between neurons, a phenomenon known as synaptic plasticity, are essential for brain function. By reshaping brain circuitry, animals learn from their experiences and adapt to their environment. Synaptic plasticity is especially relevant in sensory systems, as it allows to enhance or ignore stimuli according to their behavioural relevance. We aim to understand how sensory stimuli result in synaptic plasticity in neurons. For this, we will study responses of individual neurons in the mouse somatosensory cortex elicited by whisker stimulation, a type of sensory stimulus. A combination of electrophysiology and calcium imaging will be used to record cell activity at cellular and subcellular level. This will allow to determine which patterns of whisker stimulation result in synaptic plasticity and to study how the spatial arrangement, activation order and local interactions of synaptic inputs determine it. The observed input patterns will be replicated in neurons in brain slices and in a computational model to define the requirements for this type of plasticity. This project will help to understand the basic principles of synaptic plasticity and how sensory systems are adaptable to the environment.

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

Exploring Biological Pathways in Alzheimer’s Disease Using Polygenic Scores, MRI and Blood Biomarkers 30 Sep 2018

Studies have identified lots of small genetic changes associated with Alzheimer’s disease. They relate to disease processes like immunity, inflammation cholesterol metabolism. I aim to: - Examine small changes in groups of genes related to disease processes. I will do this by creating 'genetic scores' for different processes. - Explore associations between the 'genetic scores' and changes on brain scans, blood tests for inflammatory markers and cholesterol, and memory function. I will use information from large groups of people which has already been collected from other large studies: an in-house cohort, the Avon Longitudinal Study of Parents and Children, and UK Biobank. These include different age groups, so I can potentially identify the earliest events in the disease. My project will have unprecedented ability to detect differences because the total number of participants is so big. The findings of this study could help us to identify those who might benefit from particular treatments in clinical trials. This will help to focus efforts to find novel therapies for Alzheimer's disease.

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

Understanding the Antecedents and Outcomes of Frequent Adolescent Cannabis Use 08 Nov 2017

As cannabis policy liberalises, frequency of use is expected to increase amongst adolescents. Frequent cannabis use during this period is associated with health-related harm, including increased risks for Common Mental Disorder (CMD). Early Life Stress (ELS) is a consistent correlate of adolescent cannabis use. However, we know little about the mechanisms underpinning the development of frequent cannabis use and the nature of the relationship between frequent adolescent cannabis use and subsequent CMD. I’ll use two large longitudinal datasets (ALSPAC and VAHCS) to: Explore how ELS is associated with frequent adolescent cannabis use Identify pathways between frequent adolescent cannabis use and adult CMD To address 1), ALSPAC data will be used to explore whether cumulative ELS increases likelihood of frequent adolescent cannabis use (Longitudinal Latent Class Analysis), and whether antisocial behaviour and mental health symptoms in adolescence mediate this relationship (Causal Mediation Models). For 2), VAHCS data will be used to ascertain whether post-adolescent employment and drug/alcohol abuse are on the causal pathway between frequent adolescent cannabis and adult CMD (Causal Mediation Models). The application of new statistical developments allows novel exploration of causal pathways between frequent cannabis use’s antecedents and outcomes, which has practical utility for informing intervention.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Bristol

An investigation of the causal pathways from childhood conduct problems to poor health outcomes and criminal behaviour in adulthood 08 Nov 2017

Conduct problems (CPs) are common across childhood and adolescence and there is increasing evidence from prospective, longitudinal studies that they may impact on a wide range of adverse outcomes in adulthood including antisocial behaviour and offending, psychiatric disorders, and poor physical health. However, there is little empirical evidence regarding processes underlying the strong associations observed. Additionally, less is known about the long-term consequences of CPs in low- and middle-income countries. Using two population-based birth cohorts in the UK and Brazil, the aims of this proposal are to: 1) Examine how different patterns of CPs across childhood and adolescence relate to adverse outcomes in adulthood (criminal behaviour, psychiatric disorders, cardiovascular disease risk). 2) Test three hypothesised explanations for the associations observed, comprising: a) Exposure to ongoing adversity across the life-course; b) Shared genetic and early-life environmental risk factors; c) Potential "snares" in young adulthood (i.e. mediators of the association between CPs and adverse outcomes). The overarching goal of this research is to identify a short-list of potential intervention targets to reduce the risk of negative consequences arising from childhood CPs. Therefore, I will also conduct a feasibility study to examine the potential of modifying the intervention targets identified from the research.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Bristol
Amount: £8,000
Funder: The Wellcome Trust
Recipient: University of Bristol

Designing modular protein scaffolds to study growth factors’ synergy: how splitting modular synthetic proteins into self-assembling parts affects overall expression and structure 31 May 2018

Growth factors control the fate of stem cells but it is still unclear how their organization and synergy contributes to cell proliferation and differentiation. To study these effects, molecules that can precisely display multiple growth factors need to be developed. Modular proteins, formed by repetitive units, can be designed to have very complex structures and their length can usually be changed easily. In this project I aim to express a modular protein, which has been computationally designed, in E. coli both as a whole protein and as self-assembling peptide blocks. I will use split inteins to allow multiple peptide fragments to join and bond to produce the desired modular protein. The aim of this research is to investigate how using self assembling blocks of peptides affects the yield of the final modular protein product when expressed in E. coli and to find whether or not expressing a modular protein in the form of self assembling blocks changes its structure compared to expressing the same protein as one polypeptide chain initially. These results will help understand how to better produce modular proteins to display growth factors and study effects of signal organization on cell response.

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

Identification of deep vein thrombosis causative factors 31 May 2018

Thrombosis is defined by the abnormal formation of a clot within a blood vessel. Deep vein thrombosis (DVT), a subset of venous thromboembolism (VTE), commonly occurs within the deep veins of the legs. A variety of genetic and acquired risk factors have increased the prevalence of DVT during the past decade. Due to its somewhat asymptomatic nature, DVT can lead to complications in untreated individuals. While some research has been done on DVT, the direct causes of the disease are still relatively unknown. The purpose of this project is to identify the factors causally associated with DVT which may not have been identified through observational epidemiology. I will use an advanced causal analysis technique in genetic epidemiology called Mendelian randomization (MR) to determine what causes DVT. My first aim is to investigate what causes DVT using a hypothesis-free MR analysis. To do this I will use MR-Base - a database containing compiled GWAS summary data. I will then focus in more detail on a known cause of DVT (high BMI) and investigate what might mediate this causal effect. It is anticipated that the findings made during this project be a starting point for a prophylaxis against the outlined disease.

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

Dynamic Cell Biology 30 Sep 2017

Not available

Amount: £2,540,000
Funder: The Wellcome Trust
Recipient: University of Bristol

Understanding the Ethical Challenges in the Practice of Palliative Care in Uganda 17 Jul 2017

Aim: To explore and describe the ethical challenges faced by palliative care professionals in Uganda, and assess clinical and educational implications. Background: Palliative care services, originally developed in the UK, are being translated to locations across the world. Cross-cultural value differences must be considered in the implementation of new services, with UK models adapted accordingly. Exploring ethical challenges faced by palliative care professionals will inform understanding of the nature of these differences; and how they impact on care, and speciality training curricula. Methodology: Semi-structured interviews with Ugandan palliative professionals and regional trainees studying at Hospice Africa Uganda, to explore the ethical challenges faced day-to-day. A subsequent continent-wide online survey to examine how ethical challenges and concepts vary in content across geographical contexts. Use of empirical bioethics approaches to formulate recommendations for palliative care practice and education, with stakeholder workshops in Kampala and London to review the draft recommendations for changes in curricula in both countries. Outputs: The findings will inform evidence-based changes to palliative care ethics curricula, directly impacting healthcare training across Africa and further afield, and benefiting those who provided the data. This study will also provide research training to support a career-long body of work examining these issues.

Amount: £267,883
Funder: The Wellcome Trust
Recipient: University of Bristol

Understanding the mechanisms of Cell Competition and its role in tissue biology 30 Nov 2016

Cell competition is increasingly recognized as playing a key role in selecting the cellular composition of tissues, both in health and diseases such as cancer. My proposed research aims to advance our understanding of the mechanisms of cell competition and how it impacts on adult tissue biology, to advance our fundamental understanding of this biomedically-relevant process and learn how to harness it for therapeutics. Building on my group’s recent discoveries and methodological advances, I will use an integrated strategy combining in vitro and in vivo approaches to: 1) Elucidate how the oxidative stress response, which we found marks cells as ‘losers’ for competitive elimination, triggers cell competition in Drosophila. 2) Elucidate another link we discovered between aberrant autophagy in ‘loser’ cells and cell competition, in Drosophila. 3) Characterize the molecular mechanisms behind our discovery of p53-induced cell competition, using a CRISPR-based genomic screen in mammalian cultured cells. 4) Investigate the impact of cell competition on human adult tissue biology, using human primary keratinocytes and p53 competition-inducing mutations. 5) Carry out targeted proof-of-principle experiments to investigate for the first time whether cell competition can be exploited to improve tissue engraftment and repopulation in vivo, using the mouse airway.

Amount: £2,016,565
Funder: The Wellcome Trust
Recipient: University of Bristol

Vacation Scholarships 2017 - University of Bristol 16 Jun 2017

Vacation Scholarships 2017 - University of Bristol

Amount: £19,250
Funder: The Wellcome Trust
Recipient: University of Bristol