- Total grants
- Total funders
- Total recipients
- Earliest award date
- 10 Apr 2001
- Latest award date
- 30 Sep 2018
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
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.
Investigating the immunomodulatory effects of extracellular vesicles derived from mesechymal stromal cells 31 May 2018
My proposed hosting group has shown that mesenchymal stromal cells (MSCs) ameliorate kidney injury in mice through paracrine effects.Their preliminary work suggests that the MSCs are entrapped in the lung following intravenous administration and mostly die within 24 hours. Host macrophages are attracted to the MSCs and are stimulated to upregulate the anti-inflammatory cytokine, IL10, which suggests they are being polarised towards an anti-inflammatory phenotype (i.e. to M2 macrophages). The main aim of my project is to explore whether extracellular vesicles (EVs) released by the MSCs are responsible for mediating their immunomodulatory effects. Specifically, I will investigate whether the EVs polarise macrophages towards an M2 phenotype. The first objective will be to use a co-culture model comprising human bone marrow-derived mesenchymal stromal cells (BM-MSCs), which have already been shown to polarise macrophages to an M2 phenotype. The BM-MSCs will be co-cultured with human macrophages using a transwell culture system, and the ability of the BM-MSCs to polarise the macrophages to M2 will be investigated using flow cytometry and quantitative reverse transcriptase PCR (qRT-PCR) to determine the levels of M1 and M2-specific markers. The effect of BM-MSC-derived EVs on macrophage polarisation will then be tested.
The evaluation of appetitive odours: Exploring the role of weight status and level of satiation 31 May 2018
In the context of a global obesity epidemic, factors that may contribute to the overconsumption of energy are critical to understand. Olfaction is likely to play a key role in our evaluation of foods, particularly in identifying sources of energy (high calorie items), but this is currently under-explored. The risk profile for obesity includes greater hedonic responsiveness to food cues such as odours and a lack of diminished motivation to acquire foods even when full. This project will investigate how high calorie and low calorie pleasant food odours may be evaluated differently across healthy weight and obese individuals in either a hungry and sated condition, and if general reward sensitivity or specific tendency to reward-driven eating moderate this effect. The key goals of this project are two-fold. Firstly, the intention is to provide the student with skills and experiences that will support her appetite research career goals. Secondly, to answer the following research questions: Do high calorie odours elicit increased desire to eat relative to low calorie odours? Are weight status (NW v OW/OB) and hunger state (hungry v sated) differences apparent in appetitive responses to food odours? Does general reward sensitivity or tendency to reward-driven eating moderate these effects?
VecPrime: immune priming to vaccinate vectors 21 May 2018
Mosquito-borne diseases are hugely harmful to people and livestock. Understanding how the mosquito vectors’ immune system resists pathogen infection is crucial to understanding and controlling these infectious diseases. Despite lacking the vertebrate adaptive immune system, insects are able to retain memory of their immunological history through a poorly understood phenomenon known as immune priming. We have developed a method to effectively ‘vaccinate’ mosquitoes against the globally important mosquito-borne West Nile virus (WNV). Here, we propose to expand on our findings to understand the mechanisms and fundamental evolutionary principles behind immune memory in a medically relevant vector system. By using a powerful combination of experimental approaches we will: 1) identify the degree to which mosquito priming varies across mosquito vectored viruses, 2) test whether priming offers cross-protection against other viruses, 3) identify candidate genes responsible for priming using RNAseq, and 4) determine whether cellular responses are necessary for immune priming. Taken together, the results will identify the extent, specificity and mechanisms of priming in mosquitoes and establish a system to explore whether priming could serve as a form of disease control across a wider range of medically and agriculturally important disease vectors.
Role of STAT3 in bovine protozoan infection 31 May 2018
Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic transcription factor and signalling molecule. Whole animal knock-out mice are embryonic lethal, while cell-specific KO present with differing phenotypes including exacerbated and reduced inflammatory responses dependent on the cell type altered. Using a bovine model of protozoan challenge, we have noted an age-related difference in monocyte responses. Differential gene expression analysis indicates that the STAT3 network is more robustly activated in neonates and this corresponds with enhanced parasite clearance[CJ1] . We now propose to test the actions of STAT3 in two systems to determine if age-dependent resistance to infection is dependent on STAT3. Firstly, bovine neonatal and adult monocytes will be challenged with the abortifacient Neospora caninum; the cytokine response and parasitemia will be measured against a background of STAT3 chemical inhibition. Secondly, using a novel bovine intestinal organoid model, the role of STAT3 in N. caninum infection of the small intestinal epithelium will be tested. Differentiated organoids will be challenged under conditions in which STAT3 has been acutely inhibited, and the cytokine response and parasitemia measured. This work will determine if the differential age-related response to infection extends beyond the monocyte and is STAT3 driven.
Cell signalling involves protein-protein interactions. The most common module for binding is the SH3 domains, over 400 of which are encoded for in humans. Electrostatics play a key role between negative binding surfaces and positive peptides, but it isn’t fully known how conserved this is amongst family members. We will investigate the conservation of electrostatic binding amongst the yeast SH3 domain family and orthologs of the Abp1 SH3 domain. This will involve using domains and domain-peptide hybrids with several biophysical techniques to give us the necessary thermodynamic measurements to analyse the strength of binding and stability. We will vary NaCl buffer concentrations to investigate the stability of domains and the strength of the interaction with domain-peptide hybrids. It is hypothesized that at higher NaCl concentrations, domain stability will be stronger, however the peptide interaction will be weaker. We expect salt will affect the family members differently but overall electrostatic interactions will be conserved as an essential feature. A deeper understanding of electrostatics in peptide interactions will help us to develop peptide inhibitors to block cancerous signalling pathways and therefore be developed as therapeutics for treatment against cancers.
Investigating the role of deubiquitylases on the stability of programmed death-ligand 1 and epidermal growth factor receptor in non-small cell lung cancer 30 Sep 2018
This project will examine the relationship between two proteins: epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) relevant to non-small cell lung cancer (NSCLC). Mutations in the EGFR drive tumour growth and survival, whilst the presence of PD-L1 at the cell surface limits the effectiveness of an immune response. We will study the relationship between EGFR activity and PD-L1 expression in a model cell system, with the specific aim of identifying intermediary proteins. We will also study each protein individually with the aim of understanding the processes which set the high levels of protein displayed at the cell surface. Both proteins are validated clinical targets, but patients may acquire resistance to the existing drug therapies. Like any population, the amount of any given protein is governed by the rate of its creation versus destruction. A family of proteins called deubiquitylases (DUBs) is known to regulate the fate of specific proteins leading to either an increased or a decreased population size. We aim to identify particular DUBs that influence PD-L1 and EGFR and understand the mechanism by which they do so. By inhibiting these enzymes we will open up a new therapeutic strategy to reduce EGFR and/or PD-L1 levels.
Investigating the role of the RNA binding protein HuR in spinal tissues using a mouse transgenic model 31 May 2018
Understanding the biological mechanisms underpinning chronic back pain is essential for future development of treatments for this debilitating condition. The roles of post-transcriptional gene control in the regulation of spinal structures such as the intervertebral disc (IVD) are poorly understood. Using a conditional knockout mouse model of the post-transcriptional regulatory protein HuR, we have demonstrated that it can perform an important role in the development of the embryonic spine. Building on these findings, this vacation scholarship project will test the hypothesis that tissue-specific knockdown of the RNA binding protein HuR in the IVD of adult mice results in acute degeneration of the tissue. To do this the project has three major aims: Archived lumber spines from control and knockout mice will be processed for routine histological analysis Sections will be blindly scored for IVD degeneration. Immunohistochemistry will be used to assess the levels of HuR in IVD tissue from control and knockout mice to confirm the extent of the knockout and the specific tissues affected. This project involves a program of work that is realistic in scope for a summer scholar, provides practical and analytical research training whilst also directly complementing ongoing research in the supervisor's laboratory.
Antimicrobial resistance study to determine outcomes and transmission of extended-spectrum beta-lactamases (ESBLs) in Blantyre, Malawi (AntiDOTE) 30 Sep 2018
In Malawi, the proportion of patients who have infections with bacteria that are resistant to commonly used antibiotics is increasing. In other settings, these drug-resistant infections are associated with poor outcomes, including increased risk of death. Despite this, studies which investigate the causes and outcomes of these resistant infections in Africa are limited, and there are none currently from Malawi. I propose to follow-up patients who develop a specific type of resistant bacteria in their blood, called extended-spectrum beta-lactamase resistant bacteria (ESBL). These infections are resistant to the most commonly used antibiotics in Malawi. I aim to: Understand the causes of these infections Identify the effects, including mortality Many people in Malawi have ESBL bacteria in their digestive tracts without the presence of signs or symptoms of infection, (carriage). People who carry ESBL may transmit these bacteria to others, contributing to the proportion of patients with resistant infection. The causes of ESBL colonisation in Malawi have not been investigated. The second part of my study aims to: Take stool samples from people living in Blantyre, to investigate the proportion of people carrying ESBL Identify risk factors for colonisation with ESBL Predict ways in which ESBL colonisation might be reduced
The University of Liverpool (UoL) and its vicinity lacks in vivo nuclear and CT imaging capability for small animals. To address this critical need, we are requesting an integrated PET+SPECT+CT scanner. The proposed scanner is the only preclinical PET+SPECT+CT on the market that allows simultaneous detection of SPECT and PET probes at sub-millimetre resolution, with the additional advantage that its small foot-print will enable it to be housed within UoL’s purpose-built Centre for Preclinical Imaging. Many potential collaborative research projects cannot currently be facilitated at UoL due to the lack of this imaging capability, despite their potential for scientific excellence and for generating novel, highly impactful results. The equipment will enable users to gain unprecedented insights into the mechanisms underlying various diseases as well as evaluating the safety and efficacy of novel therapeutic interventions. If funded, the PET+SPECT+CT scanner would significantly enhance a variety of already-funded research programmes at UoL in the fields of regenerative medicine, tropical disease (snake envenoming), arthritis, cancer and pharmacology. Furthermore, by advancing UoL’s whole-animal imaging capability beyond the current state-of-the-art, the scanner will enable new projects to be developed, will spur collaboration with nearby Universities, and facilitate industry-academia collaboration in the field of preclinical imaging.
The role of endogenous transposable elements in the pathogenesis of Parkinson’s disease. 31 Jan 2017
Genome wide association studies demonstrate that Parkinson’s disease (PD) has a large genetic contribution. However, these studies also indicate that we still have much to learn about the genetic causes of PD. To explain this missing genomic component we hypothesise that endogenous non-LTR retrotransposons which are known to be active in the human genome, and in particular in the CNS, result in novel insertions that can act as both a germline predisposition variant or de novo mutation that affects the progression of PD. These non-LTR retrotransposons include Long Interspersed Elements class 1 (LINE-1, L1), Alu- and SINE-VNTR-Alu (SVA) elements. I will use DNA from individuals with PD or matched controls using a technique termed retrotransposon capture sequencing to identify both: a) Increased or novel retrotransposition events occurring in the CNS of individuals with PD which would correlate with neurodegeneration of these neurons. b) Specific germline insertions predicted to be a predisposing factor for PD.
Genome wide association studies demonstrate that amyotrophic lateral sclerosis (ALS) has a large genetic contribution and a gender bias in risk. However, these studies also indicate that we still have much to learn about the genetic causes of ALS. To explain this missing component we hypothesise that endogenous non-LTR retrotransposons, which are known to be active in the human genome, result in novel insertions that can act as germline predisposition variants or new de novo mutations. These non-LTR retrotransposons include LINE-1, Alu- and SINE-VNTR-Alu (SVA) elements. We are currently identifying novel somatic insertions in DNA from both motor neurons and lymphocytes of individuals who have died of ALS using a technique termed retrotransposon capture sequencing. This data is now available to validate, data-mine and address the functional consequences of such insertions. Particular focus will be given to insertions on the X chromosome which might in part explain the gender bias. The proposal is therefore to determine if: a) Increased or novel retrotransposition events have occurred in the motor neurons of individuals with ALS which would correlate with neurodegeneration of these neurons. b) Specific germline insertions are a predisposing factor for ALS.
The aim of this project is to develop a completely xeno-free culture system for human mesenchymal stem cells (hMSCs), cultured on synthetic peptide hydrogels (PeptieGel Design, Ltd.) and ‘mechano-cultured’ in a simple wave tank bioreactor with dynamic hydrostatic pressure acting as a dominant stimulus to control cell growth and differentiation into active osteoblasts and chondrocytes. Our hypothesis is that the changing pressure (which replicates the loading experienced during anabolic exercise) will stimulate mechanotransduction pathways in the cell that promote the growth, asymmetric division and subsequent differentiation of hMSCs by enhancing the signal transduction of autocrine and paracrine growth and transcription factors. Our project goals therefore are to: Combine a simple wave tank bioreactor with our hydrostatic pressurisation system. Culture hMSCs in synthetic peptide hydrogels as encapsulated 3D microcarrier beads. Compare growth of conventionally cultured (T-flasks) hMSCs to the bioreactor cultured hMSCs Switch to differentiation media (chondrogenic and osteogenic) to determine how hMSCs differentiate during the end stages of mechanoculture. A summary of these goals is attached in the supporting document (fig. 1.)
The proposed project is embedded in a larger neuroimaging study of 40 cannabis dependent participants. The study aims to disentangle the effects of a brief mindfulness session, relative to an active control relaxation intervention, on brain plasticity, mindfulness, craving measured immediately before and after the mindfulness or relaxation intervention; and how these changes predict level of cannabis use at 7-day follow up assessment. Immediately before and after the mindfulness intervention, neuroimaging assessment (during rest and a reappraisal task) will be conducted along with self-reported measures of mindfulness, craving and impulsivity. Before assessment, sample’s demographic characteristics, psychiatric health and cannabis use history will be recorded. The aim of the study is to establish the structural and functional changes (neuroplasticity changes) that are produced by the mindfulness intervention and to use cognitive and behavioural measures to determine the effect of the intervention on the patient’s cannabis addiction. A double blind active control will be used as a valid baseline to compare the results of the mindfulness intervention to (a feature lacking in previous research in the area) and a one-week follow up will determine whether the behavioural and cognitive changes found from the intervention are longer lasting.
Awaiting Revised Summary
The mechanical properties of the extracellular microenvironment influence the behaviour of fibroblasts. Solid tumours often exhibit changes in the stromal extracellular matrix (ECM) and tumour growth in turn is directly regulated by the stroma and carcinoma-associated fibroblasts (CAFs). However, it is not clear how signals are transduced from the extracellular matrix to the nucleus of CAFs or how this influences global cellular processes such as transcription. We have dentified the existence of a novel force transduction pathway from adhesion sites to the nucleus that is able to regulate cell migration and is required for tension-dependent changes in transcription. We will compare the adhesion and mechanical transduction properties of normal tissue fibroblasts with CAFs to identify how the tumour microenvironment influences force transmission. The aims of this project are: - Analyse the nucleo-cytoplasmic force coupling-dependent adhesome of carcinoma-associated fibroblasts - Identify how nucleo-cytoplasmic force coupling influences cell-matrix adhesion properties and functions - Investigate how beta-PIX regulates nucleo-cytoplasmic force transduction in CAFs - Determine the role of CAF nuclear force modulation on transcription and tumour cell invasion