- 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.
Proteomics is a powerful tool that is increasingly used by scientists in a wide range of biologically and medically important areas. Here, we are requesting funds for a cutting-edge liquid-chromatography mass spectrometry (LC-MS) system that will enable us to support Wellcome-funded researchers in Newcastle with access to state-of-the-art proteomics. We will utilise this instrument to enhance the research of a number of exceptionally successful clinically relevant research groups. In particular, we will perform quantitative proteomics to identify changes to the mitochondrial proteome in response to disease mutations, characterise immune populations during early human development, the role of mutations in inflammatory disease in humans, analyse molecular pathways and identify biomarkers in liver disease and fibrosis, and describe molecular mechanisms in bacterial cell biology and pathogenicity. Overall, this instrumentation will boost the research of Wellcome-funded researchers at Newcastle University.
Reactive Oxygen Species (ROS) play a dual role in cellular physiology. On one hand, ROS are damaging oxidants that have been proposed to cause ageing. On the other, ROS are essential messengers required for maintaining cellular homeostasis. The aged and sick accumulate defective mitochondria that generate high levels of ROS, but antioxidant therapies fail to improve prognosis or extend lifespan. Furthermore, increasing mitochondrial ROS levels in animals extends lifespan rather than reducing it. A new paradigm explains these contradictory results proposing that under normal physiological conditions, ROS are only produced at specific sites (e.g. mitochondria) by specific ROS generators (e.g. respiratory complex I) which regulate distinct redox signalling pathways. Conversely under pathological conditions ROS are produced at unspecific places causing oxidative stress. My laboratory has characterized the first site-specific ROS signalling pathway which regulates animal lifespan: ROS produced via reverse electron transport (RET) at respiratory complex I. This proposal will fully characterize this new redox signalling pathway by addressing three aims: (i) identify the genes and proteins involved in the initiation, amplification and neutralization of ROS-RET, (ii) understand when and where ROS-RET needs to be activated to extend lifespan, and (iii) dissect the pathological consequences of dysregulation of ROS-RET signalling.
The Seed Award is the first step in an ambitious undertaking to understand the ethical, social, policy and professional challenges faced by nurses working in police stations. Since 2003, there have been two substantial changes to custody healthcare: the introduction of a predominantly nurse-run service, and the transference of governance to private companies. No study has yet investigated the impacts of both changes on custody medicine. In order to do so, a baseline description of police nurse practice is necessary. Semi-structured interviews will be conducted with 20 nurses (each working for one of three different companies) from four constabularies in England and Wales, in order to identify the core responsibilities of custody nurses as well as key practice differences. These findings will be used to refine the research questions for an application to the Wellcome Trust Investigator Award. In addition, a Planning Meeting, involving scholars who have previously researched custody medicine or forensic nurses along with representatives from United Kingdom Association of Forensic Nurses (UKAFN), will be held. The attendees will become an Advisory Panel for the Investigator Award and it is envisaged that the outcome of the research will be of use to UKAFN in better supporting custody nurses.
Identifying Optimal Neurostimulation for Epilepsy using Computational Approaches (IONECA) 05 Sep 2017
Epilepsy is a debilitating disease characterised by unpredictable recurrent seizures. Continuous electric brain stimulation is a promising treatment option for 35% of patients that are drug-resistant. However, our understanding of its mechanisms of action is still limited, the success rates vary, and there is no clear strategy regarding stimulation location or parameters. We propose to apply network analysis and computational modelling approaches for identifying optimal stimulation settings on a patient-specific basis. In a retrospective study, we will compare the functional networks of patients with focal epilepsy during different stimulation settings, and relate these changes to the stimulation effect on seizures. We will then use computational modelling and inference to simulate patient-specific functional networks that predict the stimulation effect for settings which have not been tested in the patient. Finally, combining our simulations with optimisation methods will allow us to identify optimal stimulation parameters for each patient. In summary, we aim to develop a comprehensive network analysis and modelling framework that will help identify the "where" and "how" of continuous electric brain stimulation in focal epilepsies. This will result in an analysis software package for prospective use, which would significantly contribute towards making neurostimulation a reliable treatment option in epilepsy.
In all cells chromosome replication requires key initiator proteins to unwind the DNA at specific sites termed origins. Despite the fundamental importance of DNA replication initiation, crucial aspects of the process remain poorly understood. My vision is to identify all essential features of both the bacterial replication origin and DNA replication initiation proteins in vivo. This comprehensive reverse genetic analysis will guide biochemical investigations into the activities associated with deleterious mutations, thereby revealing the interactions and steps necessary for the physiological initiation reaction. Towards this goal I have created a bespoke tool: an inducible heterologous replication initiation system that allows construction and characterization of mutations within endogenous replication initiation factors. This methodology, combined with assays we developed to analyze DNA replication initiation in vitro, led us to identify a new essential bacterial replication origin element (Richardson et al. Nature 2016). We will build upon this successful approach and go on to develop more sophisticated heterologous replication systems, opening the door to studying all aspects of chromosome replication. Importantly, the bacterial DNA replication machinery is an underexploited drug target. Knowledge of bacterial DNA replication resulting from this work will provide a guide for disrupting this process in pathogenic species.
I aim to reveal the elusive basic principles of bacterial cell division by super-resolution microscopy. This is the next step in my long term vision to discover fundamental principles of how protein nanomachines spatially organize cells. The bacterial cell division machinery is a crucial cellular module essential for bacterial survival, and a mechanistic understanding of division is essential to understanding mode of action of cell-division-targeting antibiotics. Cell division is also a fascinating puzzle: bacteria and animal cells both use a cytoskeleton to constrict the cell; but how do bacteria, unlike animal cells, manage to do so without using any motor proteins? The mechanistic principles of bacterial cell division have escaped elucidation for decades because the cell division machinery is organized on a scale below the diffraction limit of conventional microscopy. I will overcome this problem by pushing the limits of super-resolution microscopy to reveal the organization and motion of the Bacillus subtilis cell division machinery at unprecedented resolution. This will reveal the physical mechanisms of cell division by answering three critical questions: How is the bacterial cell division machinery organized? How does it generate constrictive force? How is force generation coordinated with remodelling of the bacterial cell wall?
Mitochondrial diseases are a group of genetically heterogeneous and progressive disorders which can affect multiple organs. There are currently no curative treatments, with palliative treatments only available for some patients. A better understanding of the molecular pathology of mitochondrial diseases is needed to accelerate the development of new treatments. Evidence from in vivo models suggests that mitochondrial disease may be a result of adaptations to mitochondrial dysfunction during development, which when corrected prevent mitochondrial disease pathology. I plan to test this using Drosophila melanogaster, inducing mitochondrial dysfunction by decreasing levels of respiratory Complex I at different stages of development, in the whole fly and in specific tissues. Using this approach I will study the effects of mitochondrial dysfunction at the molecular, physiological and behavioural level. I will also test if mitochondrial disease can be rescued by restoring mitochondrial function. Finally, I will develop fly models of mitochondrial disease to establish a high-throughput screening methodology to identify novel therapies for mitochondrial disease. This combined approach will broaden our knowledge surrounding the effects of mitochondrial dysfunction and use new and existing models of mitochondrial disease to identify novel therapies. Thus, it has the potential to greatly impact mitochondrial disease research.
In this project I will measure the expression of various proteins involved in the DNA damage response (DDR) in extracts of a novel cell line that spontaneously immortalised from a primary culture of ascites cells from a patient with clear cell ovarian cancer. I will also determine the sensitivity of this cell line to DNA damaging anticancer drugs and ionising radiation, potentially also in combination with inhibitors of the DDR, e.g., ATR, PARP, using both growth inhibition and cytotoxicity assays. If time allows, I will also measure cell cycle perturbations after DNA damage. At the end of the project I will compare the cytotoxicity data with the protein expression data (and potentially the cell cycle analysis) to determine if expression levels of DDR proteins can be related to sensitivity.
I propose to examine the hypothesis that innate lymphoid cells (ILCs) mediate crosstalk between the intestinal microbiota and the reconstituting adaptive immune system in a cohort of children with primary immunodeficiency disorders undergoing haematopoietic stem cell transplantation (HSCT). I will use mass cytometry to examine the reconstitution of leukocyte populations after HSCT in a longitudinal fashion. I will characterise the peripheral blood ILC compartment in detail, including expression of activation markers, chemokine receptors and cytokines by ILC subsets ex vivo. I will measure gut bacterial diversity in longitudinally collected faecal samples and assess markers of microbial translocation. These immune and microbial parameters will be correlated with clinical features in a multi-dimensional statistical model to identify risk factors for HSCT outcomes such as graft-versus-host disease (GVHD) and gut failure. Further analysis of ILC function will be performed through in vitro studies of these immune populations to examine how they can regulate T cell responses. The impact of microbial signals and cytokines on ILC regulation of T cells will be assessed. A better understanding of ILC function in the context of immunodeficiency and HSCT may help us to develop strategies to avoid immune complications such as GVHD in some transplant recipients.
META-DAC - Managing Ethico-social and Technical issues and Administration of Data Access Committee 15 May 2017
We propose establishing a multi-agency data access committee (the META-DAC) to service several of the nation’s major cohort studies and to provide a scalable mechanism to incorporate additional cohorts in the future. From 1 May 2015, the META-DAC will manage and provide decisional oversight of access by researchers and other bona fide professionals to data and biosamples held by the initially designated studies: 1958BC, 1970BC, Millennium BC and Understanding Society and, initially as a pilot of scalability, incorporation of the English Longitudinal Study of Ageing (ELSA). The META-DAC will develop, implement and maintain all administrative and technical activities plus policies needed to realise an access mechanism that is fit for purpose given the complex biomedical/social data and samples in question. It will audit its own activity and provide regular feedback to funders and individual studies.
Immune-mediated inflammatory disease is a major and increasing cause of ill health worldwide. Effective therapy is hindered by our incomplete understanding of immune regulatory mechanisms and how to manipulate them. In this research project, we will focus on the molecular dissection of early onset immune dysregulation as a means to identify relevant genes and pathways in an unbiased way. We will use next generation sequencing to uncover causative mutations in children manifesting autoimmunity, autoinflammation and lymphoproliferation, sometimes in a familial way. We will characterize the diseased immune system in fine detail, using state-of-the-art technologies to learn as much as possible from small volumes of patient blood and tissue. We will study the role of the encoded proteins in vitro, modeling the effect of mutations and exploring the associated immunobiology. Finally we will create and study knock-in mouse models in which hypomorphic patient mutations are precisely engineered into the homologous murine gene. By these means we will gain maximal mechanistic insight from these experiments of nature, improve diagnostic and therapeutic outcomes for our patients and empower the development of new and better approaches to therapy of other immune-mediated inflammatory diseases.
Interdisciplinary Training Programme in Translational Medicine and Therapeutics at the University of Newcastle: "Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) study." 14 Jul 2014
Our goal is to develop a unique training programme in clinical pharmacology and translational medicine, delivered by academic-industrial partnerships, which combines theoretical teaching with practical application focussed on areas of existing research excellence and existing industrial partnerships with field-leading companies. The major features will be: 1) 4 year fellowships (1 year Masters of Research) in "Translational Medicine & Therapeutics" & 3 years original research PhD study) appointed following national competition. 2) Focussed on existing areas of research excellence in Newcastle and existing partnerships between Newcastle University and major European and US industrial partners. 3) Co-ordinated by the faculty management team responsible for the successful development of the academic clinical foundation, fellowships and lectureship programmes in Newcastle. Year 1- MRes: Joint University/Industry taught programme in clinical pharmacology and translational medicine core skills. Establish the core academic/industrial supervisory team. 24 week joint academic/industrial placement collecting pilot data facilitating the design of the three- year research project. Years 2 -4-PhD: 3-year research programme based on an underpinning science, proof of concept, first in man or early phase clinical study, or other studies that aim to develop and evaluate novel therapies in humans. The fellow will thus move from a solid theoretical base into "hands-on" practical experience, delivering a high quality innovative translational medicine project through an existing symbiosis between Newcastle and a relevant industrial partner
A critical aspect of the cell cycle is the maintenance of high levels of cyclin B1 at metaphase followed by its rapid APC driven destruction as chromosomes segregate. Impaired regulation of cyclin B1 at this stage of the cell cycle is firmly associated with aneuploidy. Knowledge of cyclin B1 control is largely limited to studies in mitotic cells. Here I will address for the first time whether mechanisms differ between mitosis and meiosis. Indeed preliminary data provide strong evidence to sugges t vastly differing regulation and have therefore led to the design of experiments to fully characterise this. Specifically; to determine how cyclin B1 is recognised by the meiotic destruction machinery and to detail the mechanistic implications of differential spatial control of both cyclin B1 and the APC in meiosis and mitosis. Differential cyclin B1 control mechanisms ultimately point towards the existence of meiosis specific APC activator. A key goal of this project will be to uncover its identity and detail a role in both vertebrate and invertebrate meiosis. A full understanding of the physiological process which regulate cyclin B1 and metaphase exit is important since errors are not uncommon and have a great negative impact on human health.