- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 17 Apr 2020
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
A study of antibody responses to antigens of P.falcoparam pre-erythrocytic and erythrocytic parasite stages in young Ghanaian children.
Tackling cognitive dysfunction in affective disorders: focus on monoamines and corticosteroids. 06 Feb 2007
Tackling cognitive dysfunction in affective disorders: focus on monoamines and corticosteroids This Masterclass application will be the catalyst in the creation of a Special Interest Group with the aim of promoting interest and collaborative research into the cognitive dysfunction in affective disorders. The application includes three interrelated phases. Phase 1 will be the creation of an interactive web site, phase 2 a two day residential meeting and phase 3 the publication of consensus statements and the application for funding for further meetings and research grants to further the aims of the Special Interest Group. The Masterclass will cover four main areas: 1) defining and measuring the cognitive dysfunction in affective disorders; 2) modelling the relevant cognitive domains in the laboratory; 3) understanding the mechanisms underlying cognitive dysfunction in affective disorders; 4) examining cognitive dysfunction as a therapeutic target.
Working memory signal in prefrontal cortex: local network interactions, layer dependence and neuropharmacology 10 Feb 2014
The project aims to elucidate how subdomains within the prefrontal cortex inteinteract during execution of a working memory task, and how these interactions are gated by dopaminergic and cholinergic neuromodulation. We will map the representation of saccade space in the dorsolateral prefrontal cortex (DLPFC) and map the (local) functional connectivity between domains therein by means of fMRI. We will then target functionally connected locations/columns and rcuirecord across cortical layers (laminar electrode recordings) while an animal model performs a working memory task (memory guided delayed saccade task). These recordings will be performed without and with simultaneous local infusion of selective dopaminergic and cholinergic receptor antagonists and agonists. The key goals are: (1) To understand to what extent functional connectivity (measured by means of resting state fMRI and task related fMRI) within the prefrontal cortex maps onto similarity of function (measured by means of electrophysiological recordings). (2) To understand the flow of information within and between canonical microcircuits in the DLPFC and how this enables the maintenance of working memory signals. Specifically, we aim to understand how the flow of information is gated in andbetween different cortical layers and to understand the neuropharmacology thatgoverns gating and interactions between different local networks.
Investigating the different roles of interneuronal populations in modulating cortical dynamics 10 Feb 2014
Normal and pathological brain activity is characterised by changes in brain rhythms. Such changes are linked to attention, sleep-wake cycles, or epilepticseizures. During an epileptic seizure, for example, there are a series of transitions which are often highly stereotyped in individuals, and which may be pathognomonic of the seizure type. There are various animal and computational models for generating oscillations in specific frequency bands. However, the transition between frequencies is not well understood. Cortical layers might show distinct frequencies that interact and lead to altered frequencies in following time steps. Furthermore, input from thalamus, corpus callosum or adjacent cortical areas might trigger frequency transitions. This project will use optogenetics to change input and on-going activity in specific circuits to test their influence on frequency transitions. Experiments will be complemented by computational models of cortical circuits to better understand on-going dynamics and inform the selection of future targets for experimental stimulation. This work will not only be important in assessing transitions in epilepsy (e.g. from the inter-ictal to the ictal stage), but also for models of external interventions to change pathological brain rhythms in the future.
A study of the interactions between proteins involved in chromosome segregation in Bacillus subtilis using the yeast-two-hybrid system 27 Apr 2017
During sporulation in the bacterium Bacillus subtilis, one of the sister chromosomes is translocated into the developing prespore. This mechanism is a useful model for studying chromosome segregation, a process which is vital in all organisms. The exact mechanism of chromosome segregation in sporulating B. subtilis is not fully understood. A protein complex, involving many proteins including Soj, Spo0J, MinD, MinJ, RacA, ComN and DivIVA, is known to anchor the origins of the sister chromosomes at opposite cell poles. We propose to test the direct interactions between members of this protein complex using yeast-two-hybrid assays. To begin with we will test interactions between the proteins Soj, Spo0J and MinD. Each of these are known to form dimers, and results from genetic and cell biology studies show that interactions between Soj-Spo0J and Soj-MinD are important for the anchoring of the chromosome origins to the cell poles. These latter interactions have not been shown directly and we aim to test these in this project. The project will hopefully move on to test further protein interactions in the complex, including those with RacA and ComN. Any interactions observed between these proteins will further our understanding of chromosome segregation in B. subtilis.
Characterization of the role of C12orf65 in quality control of human mitochondrial protein synthesis. 27 Apr 2017
I intend to determine the role C12orf65, a member of the mitochondrial translation release factor family, plays in mitochondrial quality control. Professors Zofia Chrzanowska-Lightowlers and Bob Lightowlers have recently established a technique for mitoribosomal profiling. They have already produced sets of profiling data for control fibroblasts and those artificially depleted of C12orf65 but want to compare this data to cells from a patient with a pathogenic mutation of C12orf65. My project is to learn how to interpret this data and to generate a new library from a patient cell line. Goal 1 - be trained in how to produce and interpret large datasets generated from isolated RNA fragments protected by the mitoribosomes in patient fibroblasts (weeks 1-6). Goal 2 - initiate bioinformatic studies for the interpretation of large dataset produced from a library of short protected RNA species (week 1-6). Goal 3 - prepare protected RNA fragments for library production (week 3-4). Goal 4 - produce a cDNA library from the isolated RNA fragments to allow HiSeq NextGen sequencing (week 5-6). Although I will not be able to assess data from my library, I will be constantly in contact with the Chrzanowska-Lightowlers laboratory who will inform me of the outcome.
Feeling Sound 27 Apr 2017
This proposal addresses fundamental questions about the basis of multisensory integration for touch and hearing in humans. Previous psychophysical studies in the supervisor’s lab have demonstrated interactions between amplitude-modulated sound and visual stimuli. Specifically, the ability of subjects to discriminate the amplitude-modulation depth in sounds is influenced by simultaneously watching a video of a shape expanding and contracting at the same rate as the sound modulation. The aim of the current study is to test the hypothesis that a similar multisensory interaction occurs between sound and tactile stimuli. Subjects will discriminate the depth of amplitude modulated tones (carrier frequency 250 Hz; modulation rate 2 Hz). In some cases these sound stimuli will be accompanied by a tactile stimulus in the form of a vibration delivered to the index finger with the same (2 Hz) or different (1Hz) frequency of modulation as the sound stimulus. By determining psychophysical thresholds for the sound discrimination under different conditions we will establish whether the tactile stimulus enhances or diminishes the perceived sound modulation. A second experiment will address the reverse condition, namely does sound influence tactile discrimination. The project is an ideal vacation project, because it provides the student with an independent, self-contained project.
The telomere cap in budding yeast. 14 Oct 2010
To define the roles of different proteins at telomeres of budding yeast we aim to understand: 1. Roles of specific gene products at uncapped telomeres. We will carefully analyse the effects of specific gene products on growth, cell cycle progression, checkpoint kinase activation, ssDNA accumulation and other processes in yeast cells containing uncapped telomeres. Through such experiments we will infer the in vivo biochemical function of the corresponding gene products. 2. Telomere repli cation. We will use a number of complementary methods to understand the interaction between the DNA replication fork and the telomere cap. We will address whether the newly synthesized 5' lagging strand, the previously synthesized 5' strand, or both are degraded after telomere cap failure. 3. Genes affecting the telomere cap and telomere replication. We will apply Quantitative Fitness Profiling (QFP) to tens of thousands of robotically generated double mutant yeast strains with telomere or D NA replication defects. We will extend QFP to telomerase deficient cells and to quantify the effect of over-expression libraries on the growth of cells with a telomere capping mutation. We will develop QFP algorithms and computational architecture, utilizing more advanced statistical and visualization techniques, to extract more value from the experimental screens.
Differential regulation of NF-κB activation and function through RelA Ser42 and 45 phosphorylation 27 Apr 2017
NF-kappaB transcription factor activity can be regulated by a wide array of post-translational modifications that allow integration with parallel signalling pathways, leading to differential functionality in different contexts. Published data supports an important role for RelA Ser42 and Ser45 phosphorylation as regulators of NF-kappaB function but experiments performed to date have been limited and many questions remain unanswered. However, our analysis of the structure of a RelA/p50 heterodimer to DNA indicates that these residues are not close to the core NF-kappaB consensus binding site but rather are in proximity to the DNA flanking these sites. This suggests a potential modulatory effect on NF-kappaB DNA-binding rather than total inhibition, possibly regulating target gene specificity in a temporal manner following activation. This vacation studentship project will test this hypothesis and (1) Investigate whether RelA Ser42 and Ser45 mutations have gene specific effects on NF-kappaB regulated transcription; (2) Determine the effect of RelA Ser42 and Ser45 mutations on cell viability following NF-kappaB induction; (3) Develop a system using CRISPR/Cas9 mediated genome engineering to target the Ser42 and Ser45 residues in endogenous RelA. Data from these experiments will provide insight into regulation of NF-kappaB and its role in cancer and inflammatory diseases.
Modulation of intestinal epithelial cell signalling by selenium and glutathione peroxidases. 22 Feb 2007
Selenium is a micronutrient essential for human health. Dietary intake in the UK is suboptimal for health but the implications on disease susceptibility have not been defined. The proposed work addresses whether selenium, through the selenoprotein glutathione peroxidases, modulates inflammatory signalling pathways in colonic epithelial cells and their response to microbial challenges, and how a SNP in the glutathione peroxidase 4 gene influences these mechanisms. The effects of selenium status on inflammatory signalling pathways in Caco-2 cell lines will be assessed using targeted gene arrays, measurements of NF-KB and specific pro-inflammatory cytokines. In addition, knock-down studies using siRNA and antisense vectors will define the roles of the glutathione peroxidases 1,2,4. Since microbe-epithelium interactions are critical modulators of the inflammatory pathways, the effects of Se status and GPx1,2 and 4 knock-down on the ability of epithelial cells to respond to oxidative and microbial challenges will be investigated. A common SNP in the GPx4 gene has been linked to ulcerative colitis and leukotriene metabolism and a further goal will be to define the effects of the T and C variants of this GPx4 SNP on inflammatory pathways and responses to microbial challenges using over-expression studies in Caco-2 cells.
Celebrating the Collector: Cataloguing and Curating the Papers of Professor Frederick Charles Pybus. 20 May 2014
The project's primary aim is to provide greater access to and discoverability of the papers of Professor Frederick Charles Pybus (1883-1975). A distinguished clinician and researcher, Pybus expounded quite radical theorieson issues such as cancer and its causes, and yet is better known as a book collector than for his clinical accomplishments. We will employ a qualified Archivist for a year to produce an archival standard, web-based catalogue of this archive to be hosted locally and on the Archives Hub to unlock the research potential for medical humanities researchers. These resources will be enhanced by digitising items from the archive with appropriate metadata for remote access. The work will be closely supervised by the Principal Applicant and Co-applicant, both Archivists experienced in cataloguing significant medical archives. This project will also include preservation and conservation scoping. We will commission a report by a Conservator to identify any remedial action which thepapers require and repackage using archival standard boxes and supplies. Engagement activities will be co-ordinated by the Project Archivist to promotethe existence and use of the catalogued resource to academic and clinical researchers and the general public. This will include a project blog, an exhibition with accompanying public talk through the Pybus Society, and a dissemination symposium with speakers from Newcastle University's Northern Centre for the History of Medicine and Northern Institute for Cancer Research,as well as parties from national medical and humanities bodies reflecting on the archive's significance to their particular field of expertise.
Understanding the role of autophagy in the pathogenesis of AMD using a patient specific iPSC model 27 Apr 2017
AMD remains the most important cause of blindness in the elderly. The number of AMD affected people in UK is expected to rise to 1.3 M by 2050 with healthcare costs rising to £16.4 billion during 2010-2020. Currently there is no effective treatment hence a huge unmet need for investigations into therapies. This project aims to contribute to the identification of the underlying causes of AMD by interrogating a new cell model created by the host lab. Preliminary data suggest that autophagy, a process by which the cells remove waste products, is impaired in retinal pigmented epithelial cells derived from patients with AMD, leading to deposition of waste products and increased stress. Using this model, I will investigate which step of the autophagic process is not functioning properly in retinal cells, thus leading to a better understanding of AMD etiology. To date, small molecules that regulate autophagy are used in clinical trials of other neurodegenerative diseases. By the end of this project we will find out if the existing small molecules restore the autophagy in retinal cells of AMD patients. This will contribute to the design of preclinical studies for preventing further progression of AMD and restoring sight loss.
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.
'Approaches to Ancient Medicine 2007' conference to be held at Newcastle University from 3-4 September 2007. 28 May 2007
Meetign : Approaches to Ancient Medicine 2007, Newcastle University, 3-4 September 2007.