- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 25 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Our project investigates health risks, medical interventions and health care in English and Irish prisons between 1850 and 2000. The two systems were interconnected in terms of administrative development and the high number of Irish prisoners in English prisons, yet varied in terms of the size of their respective populations, the impact of religious bodies on reform and in the role of political prisoners in shaping health. The largest research strand explores the high incidence of mental illness amongst prisoners and the impact of the prison system on the mental health of inmates, adults and juveniles, key issues which have preoccupied prison medical services and reformers from the early nineteenth century to the current day. Further strands examine the management of medical care and disease; responses to HIV/AIDS in prisons; the impact of political prisoners on medical regimes and prisoners' rights; the health of women prisoners; and the campaigns of lay and religious reformers in see king to improve facilities. The project interrogates inherent tensions as medical staff grappled to maintain healthy and hygienic practices, while devising regimens to discipline and rehabilitate prisoners in the context of poor conditions, official disinterest and intermittent overcrowding. Our case studies also consider the categories of gender, sexuality, class, age, religion, race, migration and ethnicity and how these influenced medical interventions. Alongside the production of scholarly o utputs, and a wide range of public engagement activities, our project will address current policy debates on prison systems, medical ethics and the management of prisoners' health.
Defining mycobacterial host-pathogen interactions: the role of the secreted protein MPB70 31 Jan 2017
Tuberculosis is an infectious disease which in humans is caused by Mycobacterium tuberculosis and in cattle by Mycobacterium bovis. The genome sequences of these two bacterial species are 99.95% identical, with deletion of genetic information leading to a reduced genome size in M. bovis and no unique genes per se in M. bovis compared to M. tuberculosis. The high degree of genetic identity contrasts with the distinct host preference of the pathogens, and suggests that host preference is likely driven by differences in the expression of key genes between M. tuberculosis and M. bovis. We are particularly interested in two genes coding for secreted proteins, MPB70 and MPB83, which show significant differential regulation between the two species. Through combined in vitro infection assays with bacterial mutants, proteomics studies and in silico evolution studies of these genes and their regulon, we will investigate if MPB70 and MPB83 play a specific role in the host-pathogen interaction and the nature of this interaction. By elucidating the role of these proteins in host preference, we hope to increase our knowledge of host-pathogen interaction and to open new avenues for the development of disease control approaches in both human and bovine tuberculosis.
Genome evolution in the Candida clade 31 Jan 2017
The CUG-Serine clade, a group of yeasts including the common human pathogen Candida albicans, has been known to translate the codon CUG as serine instead of leucine for over 20 years. Recently, a sister species that translates CUG as alanine was discovered. In my bioinformatics rotation I discovered a second, independent CUG-Ser clade as well as a CUG-Ala clade and three separate CUG-Leu clades.In my PhD project I will examine tRNA gene evolution in these clades and test the hypothesis that they descended from a catastrophic event in their common ancestor in which the CUG- decoding tRNA was lost. I will perform experiments to artificially push a yeast species to change its CUG translation from Ser to Leu by replacing a tRNA gene, and monitor the effect on the proteome. In parallel, I will study centromere evolution in yeasts, which show an extraordinary diversity of centromere types, by using ChiP-seq to find centromeres across the Candida clade and beyond. This project will develop valuable new tools for manipulating Candida genomes, including transformation vectors that completely lack CUG codons and should work in any species, and potentially also new centromere-based plasmids for use in C. albicans.
Streptococcus gallolyticus is a gram positive gut commensal that can cause Infective endocarditis (IE) a heart valve infection. Unusually, in the case of S. gallolyticus, patients presenting with infective endocarditis are also found to have colonic abnormalities i.e. colorectal cancer. It is thought that the presence of colorectal cancer allows translocation of the pathogen from the gut lumen into the bloodstream. To date, there is limited information on the virulence factors of S. gallolyticus that contribute to the pathogenesis of IE. This study aims to (1) identify common virulence factors in clinical isolates of S. gallolyticus from bloodstream infections and IE. This will be achieved by sequencing and de novo assembly of the genomes of 50 clinical isolates from Ireland, France, Italy, Spain and the US. The relatedness of these strains will be analysed and virulence factors identified. (2) Genes encoding these virulence factors will be deleted and the ability of the mutant strains to adhere to platelets, trigger platelet aggregation and adhere to colonic epithelial cells will be tested. (3) These genes will also be cloned into expression vectors and expressed in a surrogate expression host to analyse any gain of function conferred.
Prisoners, Medical Care and Entitlement to Health in England and Ireland, 1850-2000: Provision for Public Engagement 30 Apr 2017
An investigation of the molecular mechanism of invasion of human epithelial cells by Campylobacter jejuni using a novel in vitro model based on altering bacterial DNA topology 27 Apr 2017
Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the world. The organism is endemic in chickens where it appears to act as a commensal and is found in high numbers as part of the mucosal microbiome. In contrast the organism is highly pathogenic in humans where it displays an invasive phenotype which results in severe gastroenteritis and damage to the epithelium. The mechanism by which this important human pathogen invades the human epithelium is relatively poorly understood compared to other invasive pathogens primarily down to the fact that the organism invades at a relatively low frequency in vitro. Some studies have suggested the involvement of host cytoskeleton rearrangement whereas others have contradicted these findings. The Ó Cróinín laboratory have recently published data showing that invasion is induced by relaxation of DNA supercoiling using sub-inhibitory concentrations of novobiocin and that this results in a dramatic increase in invasion. The aim of this project is to use this induction of the invasive phenotype to study the interaction of C. jejuni with human epithelial cells in vitro and in particular to study the involvement of actin, tubulin and other host cell cytoskeleton molecules in this process.
Financial support is requested to assist the organisation of a two-day international symposium entitled 'Medical training, student experience and the transmission of knowledge, c.1800-2014' at the Humanities Institute, University College Dublin on 17-18 October, 2014. The main aim of this conference is to examine the theme of medical training and education, broadly conceived. There has not been a conference on the history of medical education since 1992, and this conference will represent the mo st cutting-edge research in the history of medical education in a variety of contexts and international settings. Considering recent concerns over standards of medical education the conference is timely. Moreover, there has never been an interdisciplinary conference on this theme. This conference will bring together not only historians of medicine, but also researchers working in related fields in the humanities, social sciences and medicine. It will allow for in-depth discussion in a relaxed bu t structured environment, with speakers being drawn from American, French, Irish, and British universities. Funding has already been attained from the Irish Research Council to cover accommodation expenses for speakers and conference catering costs. Funding is requested from the Wellcome Trust to contribute towards the travel expenses of the speakers.
Mycobacterium tuberculosis (MTB), causative agent of tuberculosis (TB), is oneof the most successful pathogens in the world. MTB is an obligate human pathogen, having no known reservoir outside of the human host. However, the related clinically relevant smooth tubercle bacilli (STB), such as Mycobacterium canettii, seems to survive in an unidentified environmental niche. Genome sequencing has revealed great diversity across STB compared to MTB, with large numbers of single nucleotide polymorphisms (SNPs) and insertion/deletions. This raises questions about the evolution of pathogens, their adaptation to pathogenic or opportunistic lifestyles and comparative analyses across these species offer an ideal opportunity to explore these phenomena. Our hypothesis is that by studying the transcriptomic response of MTB and STB to environmental stimuli we will shed light on the evolution of these pathogens and niche adaptation. We will incorporate transcriptome data with genome data of these species to see whether there is evidence for selection of
Ribo-regulation in Mycobacterium abscessus 24 Jun 2013
Characterization of regulatory RNAs (such as sRNAs) in mycobacteria is still developing, however demonstration of their differential expression under environmental stress and regulation of virulence by two-component systems suggest a role for such agents in pathogenesis. In order to characterize the regulome of M. abscessus, it is the intention of the project to generate and subsequently analyse a number of different data types including, RNA-seq, which characterizes the transcribed portion of the genome, and differential RNA-seq,which facilitates the identification of transcriptional start sites (TSS). In addition, in orderto identify the coding
Differential analysis of the genomic and transcriptomic mechanisms governing the intracellular life of atypical pathogenic Salmonella serovars in human and murine macrophages 16 Jul 2012
The aim of this project is to characterise and compare the ability of atypicalSalmonella serovars to survive and replicate following phagocytosis by both human and mouse macrophages. Salmonellosis is a zoonotic disease of major public health concern. Salmonella infections in humans have been mainly studied in the mouse model using Salmonella Typhimurium. However, the immunological response to Salmonella Typhimurium is completely different in humans to that of mice. Despite this, monocyte and macrophage studies have traditionally been carried out in murine cell lines (J774 and RAW). The interactions between a set of atypical Salmonella serovars and both human and mouse macrophages will be assessed at the bacterial and host level throughcell infection, cytokine detection/quantification and macrophage activation assays. SMRT sequencing of a specific serovar with an unusual infection phenotype will be performed to aid in genome assembly and to determine the methylome. dRNA-seq will be used to functionally annotate the genome and RNA-seq will be used to characterise the transcriptional landscape of the selected serovar. A TraDIS library will be generated for the specific Salmonella serovar to determine the essential gene set in in vitro and ex vivoconditions to identify the genes essential to survival in macrophages.
This research hopes to ascertain the effect of the Human T-Lymphotropic Virus Type 1 (HTLV-1) Basic Leucine Zipper (HBZ) protein on Interferon Regulatory Factor 7 (IRF7). The first objective is to determine the intracellular localisation of HBZ and IRF7 in HeLa cells. To achieve this HeLa cells will be grown on glass slides and transfected with plasmids encoding GFP-HBZ and FLAG-IRF7. IRF7 expression will be detected using an antibody against IRF7 followed by a secondary antibody linked to ALEXA-595 (Red). The localisation of proteins in the cells will be visualised using a fluorescent microscope. The second objective is to map the domains in HBZ that are involved in binding IRF7. To achieve this 293T cells will be transfected with plasmids encoding FLAG-IRF7 together with plasmids encoding HBZ-HIS wildtype or HBZ deletions HBZDAD-HIS, HBZDCD-HIS and HBZDbZIP-HIS. Co-immunoprecipitation assays will then be carried out using FLAG resin and precipitates will be analysed by Western Blot.
To investigate the impact of dietary fats on Alzheimer's disease-related inflammatory changes 01 Apr 2016
Obesity is a low-grade inflammatory condition and a major risk factor for age-related cognitive decline, including dementia and Alzheimer’s disease (AD). Inflammation in the brain, regulated by microglial cells, is characteristic of these conditions and may contribute to obesity-related dysfunction. The infiltration of peripheral immune cells into the brain is also implicated in this inflammatory state. The AD-associated beta-amyloid peptide (Abeta) also accumulates in the brain and circulation of obese individuals. Abeta induces the same response as some bacteria; biasing microglia towards a pro- rather than anti-inflammatory state. Diets rich in saturated fats (SFA) impact negatively on health, while the benefits of unsaturated fats are well known. This extends to the brain, as polyunsaturated fats (PUFA) promote cognitive function. PUFA are of limited therapeutic use as they are not a viable dietary replacement for SFA. Monounsaturated fats (MUFA) primarily constitute the ‘Mediterranean diet’, and are contained in many health-promoting foods. MUFA can alleviate SFA-induced inflammation, but their ability to mediate the inflammatory response in the brain, or potential to promote neurological health under obesogenic conditions have not been determined. We will evaluate whether SFA primes Abeta-induced activation of glia and macrophages, and further assess whether MUFA may alleviate Abeta-induced inflammation.
Suicide and Stigma in an Indigenous Ethnic Minority: Engaging Irish Travellers with Lived Lives. 14 Jan 2015
Suicide is a significant public health concern, associated with stigma. Young men, mental illness sufferers, prisoners and indigenous ethnic minorities bear an increased suicide risk. Irish Travellers are an indigenous ethnic minority with social and cultural parallels with similar groups internationally (Inuits, Aboriginals, Maoris, etc). Travellers experience racism and discrimination, with elevated suicide rates (x7 national average for males) and associated stigma. Traditionally their nomadi c lifestyle and limited literacy made them hard-to-reach . Nowadays they are frequently under-served and excluded from research, impacting health research and intervention. Nevertheless, we recently described methods to document their health risks (including suicide) with 80% response rates (All Ireland Traveller Health Study). Using collaborative science/arts research methods (Lived Lives) we devised methods for studying suicide and its aftermath which safely engages bereaved at-risk communiti es, the public and suicide prevention policy-makers. The Lived Lives exhibition, with artist and scientist, co-curated by communities, has facilitated dialogue and response, described as transformative. Following collaborative pre-planning with Traveller leaders and youths, Lived Lives will be transposed into Pavee Point, the national Traveller resource centre, manifesting privately and publicly, and documented over 7 days (Autumn 2015). Outputs will include an interactive exhibition and learnin g materials about suicide and its aftermath among indigenous ethnic minorities such as Travellers. The project will be evaluated by feedback from participants and expert evaluators to assess how it relates to suicide in their community, how it has shaped their understanding of suicide and its impacts, and its relevance to other socio-cultural contexts, nationally and internationally.
Non-coding RNAs and HIV-1 latency 31 Aug 2011
After decades of research, overcoming HIV-1 post-integration latency remains imperative. When HIV-1 genome integrates into the host, it behaves as a mammalian gene and it is subject to the same mechanisms controlling host gene expression. Gene silencing is a complex and multifactorial process that can beepigenetically mediated, involving steps such as chromatin remodelling, DNA methylation and histone modifications. Non-coding RNAs (ncRNAs) are well established players in this process at the host level, however, its role in HIV-1 proviral silencing is yet to be described. This project aims to address this gap and, combining in silico techniques with molecular virology based assays, explore ncRNA species role in HIV-1 post-integration latency. We will begin with in silico screening for ncRNAs that demonstrate sequence specific affinity to the HIV-1 promoter. After selection, the most promising candidates will go into function validation assays and their effect on HIV-1 transcription will be assessed. Following, wewill experimentally validate 5'LTR sequence targeting and carry out a
The molecular pathogenesis of the metabolic toxicities associated with HIV infection and therapy 31 Aug 2011
Metabolic complications are estimated to affect up to half of all HIV positiveindividuals receiving therapy. These metabolic dysfunctions primarily affect adipose tissue function; they include abnormalities in fat distribution, dyslipidemia and insulin resistance. A number of the agents used in antiretroviral therapy (ART) regimens are linked to the development of these metabolic disorders. Particularly associated are the antiretroviral classes ofnucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). Accurate knowledge concerning how antiretroviral agents act in the body and how they lead to toxicity is critical not only for the development of safer therapies but also for the design of successful ART regimens by the clinician.The key goals of the proposed project are: " To define the specific in vivo effect of PI therapy and NRTI therapy, individually and in combination on adipose tissue using transcriptomic methods.
Grant to Norfolk Knitters and Stitchers 20 Mar 2015
as a staff grant towards the running costs of an organisation which brings people together to knit and sew for good causes