- Total grants
- Total funders
- Total recipients
- Earliest award date
- 27 Apr 2006
- Latest award date
- 16 Jul 2018
- 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.
Streptococcus gallolyticus (S. gallolyticus) is commonly found in the gastrointestinal tract of ruminants. Interestingly it can cause endocarditis in humans by translocating through the GI tract at sites of colonic cancer lesions. Studies have indicated that S. gallolyticus is an excellent colonizer of the intestinal tract, forming strong biofilms via effective adherence properties (Abdulamir et al 2011). However little is known about what mechanisms these bacteria use to colonise the gut and invade the bloodstream. We have assembled a cohort of bloodstream isolates from patients across Europe and are sequencing their genomes. This project will characterise the biofilm forming capacity of the strains and compare the phenotypes of the strong and weak biofilm forming strains in growth conditions that mimic the environment of the colon (anaerobic and rich in bile salts). We will then test representative strains from the strong and weak biofilm forming groups to bind to and invade colonic epithelial cells in order to see whether biofilm forming capacity has an influence on colonic cell adherence and invasion. Finally we will test these strains for translocation across a colonic cell monolayer to see whether biofilm production by S. gallolyticus can facilitate invasion of the gut mucosa in humans.
Candida species are the leading cause of opportunistic mycoses and a common cause of nosocomial bloodstream infections (Wisplinghoff et al., 2004). Candida tropicalis is a significant cause of candidiasis, particularly in tropical regions (Pfaller and Diekema, 2007). However, much remains unknown about the origins and virulence mechanisms of this pathogen. Previous studies of pathogenic organisms have focused on detailed analyses of single isolates. However, recent work using multiple isolates of Candida albicans has shown that specific virulence phenotypes are associated with specific clades (Pujol et al., 2004; MacCallum et al., 2009; Hirakawa et al., 2015). Some previous studies using multilocus sequencing typing to investigate population structure and phenotypes of C. tropicalis have generated conflicting reports (Chou et al., 2007; Desnos-Ollivier et al., 2008; Magri et al., 2013; Tavanti et al., 2005a). In this study, we will use whole genome sequencing and detailed phenotype analysis to compare at least 50 isolates of C. tropicalis from environmental and clinical sources. We will assess the correlation between genotype and phenotypic profile, using both in vitro and in vivo virulence assays.
Computational analysis of gene clusters from antimicrobial producing and pathogenic bacteria. 31 Jan 2017
This project will develop a novel method for the in silico prediction of the function of bacterial genes based on the analysis of their genomic neighbourhood, with a specific focus on genes of interest in infection biology. Indeed, bacterial genes involved in the same cellular "macro-function", such as a signalling or biosynthetic pathway, are often physically clustering together on the genome. The computational analysis of these gene clusters could help to uncover the role of currently uncharacterised genes in certain pathways. The prediction method will be developed and tested on a dataset of publicly available bacterial genomes. Then, it will be applied to the analysis of clusters putatively involved in the synthesis of peptide antimicrobials or in processes targeted by known antibiotics. Orthologous clusters will be compared to identify protein domains that tend to co-occur in similar clusters ("domain correlation"). However, sometimes two alternative domains may fulfil the same biochemical function. In such a case, these two domains may be present as alternatives within functionally related clusters. This results in an "anti-correlation" of these domains within that cluster. The final aim of this analysis will be the identification of new antimicrobial processing enzymes and possible novel drug targets.
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.
Bovine Respiratory Syncitial Virus Vaccine 27 Apr 2017
Bovine respiratory syncitial virus (BRSV) is a leading cause of enzootic pneumonia in calves and significantly contributes to the Bovine Respiratory Disease Complex found in feedlot cattle. It is proposed to develop a new vaccine using the Semliki Forest Virus (SFV) virus replicon particle (VRP) vaccine platform. The SFV VRP is a promising vaccine platform, due in part to its efficacious immunogenicity in cattle and its ability to express protein to high concentrations in the cells it infects. Furthermore, the replicon vectors are single cycle, propagation-defective particles that are not able to spread beyond the initial infected cells. The BRSV fusion (F) protein is known to be immunogenic thus making it a good candidate protein to target for gene expression. It is proposed to clone the F protein sequence into a VRP expression plasmid in place of the SFV structural proteins. The proposed project will involve generating the VRP plasmids, generation of VRP stocks and confirmation that this VRP can express the F protein. Human respiratory syncitial virus (hRSV), a closely related virus of human importance, also expresses the F protein. Thus BRSV infection in bovines is a relevant model for hRSV, as there is no current efficacious vaccine available.
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterised by degeneration of the longest motor neurons which leads to muscle weakness and spasticity in the lower limbs. There are currently no treatments to cure or even to slow the course of these diseases. In this project I will test a novel in vivo model of HSP generated by CRISPR/Cas9 gene editing in Drosophila. I will investigate gene and protein expression, locomotor behaviours and motor neuron endoplasmic reticulum (ER) organisation. My research will determine how HSP-causing mutations affect endoplasmic reticulum organisation and neuronal function. The results from this project will validate a novel model of HSP and will further our understanding of the molecular mechanisms underpinning this neurodegenerative disorder.
Influence of Diet in Heart Failure: Role of Short Chain Fatty Acids in monocyte phenotype 27 Apr 2017
The aim of this project is to find out if small chain fatty acids (SCFA's) play a role in heart failure via their interaction with inflammatory cells and the regulation of inflammatory cytokine production that can lead to fibrosis and diastolic dysfunction. SCFA's are produced by the gut microbiota following the fermentation of soluble fibres that are contained in the diet. There is evidence of dramatic changes in gut microbiota populations in patients with heart failure and a clear link between heart failure and the amount of fibre in the diet. The presence of free fatty acid receptors (FFAR) on monocytes might link SCFA with the release of inflammatory cytokines possibly leading to progressive damage of the cardiovascular system. FFARs are expressed on monocytes and macrophages. This project will firstly quantify FFAR3 expression in a cohort of 44 patient-derived monocyte cDNA samples. FFAR3 expression will be correlated with previously aquired data on FFAR2 and inflammatory gene expression and serum cytokine data. Monocytes and macrophages are known to be the major drivers of inflammatory and fibrotic processes in heart failure. This project will investigate the role of SCFA's in regulating human macrophage differentiation in response to known drviers of M1/M2 phenotype.
The effect of mucus and mucin Pseudomonas aeruginosa phenotype and interaction with host cells 16 Jul 2012
Pseudomonas aeruginosa colonises mucus in the lungs of individuals with CF resulting in chronic respiratory infections. We will examine how the bacteria respond to the presence of mucin/mucus and whether or not this response has aneffect on expression of mucin binding proteins and on virulence. We will collect data on the differential expression of Pseudomonas Outer Membrane Proteins (OMPs) in response to both the presence of mucin and mucus and the interaction with host cells. Effect of co-culture of the organism with mucus secreting cells and with purified mucin on OMP expression will be examined using SDS PAGE and affinity blots. The role of these proteins in mediating interaction with mucin and glycans will be assessed using mucin affinity blotting, neoglycoconjugate arrays and a novel microarray platform. Bioinformatics techniques will be used to predict Pseudomonas OMPs that have lectin-like properties. This will aid us in identifying protein properties andmotifs that are responsible for facilitating the binding of proteins to glycans. We also propose to use global transcriptional analysis of selected strains of P. aeruginosa by RNA seq grown in the presence and absence of mucin. The biological relevance of bioinfromatic findings will be assessed in the lab.
The aim of this project is to identify Escherichia coli gene signatures which can be used to classify pathogenic strains. Recent outbreaks have shown that there is a need for rapid identification and subtyping of pathogenic strains in real time. We will construct and leverage the power of the E. coli pan genome by grouping all genes across the available E. coli genomes (environmental, pathogenic and commensal strains) into core, accessory and distributed gene sets. This will define an E. coli species-wide gene pool which will facilitate the detection of gene combinations associated with pathogenic strains. The incorporation of genome data from other species that display similar modes of infection or inhabit similar environments will generate corss species correlog information and widen the scope of our findings. In addition to the pan genomic approach, the methylation profile of E. coli serotypes will be determined using SMRT sequencing to provide insights into the role methylation plays in virulence. The project will mostly consist of bioinformatics analysis with lab work including the preparation of samples and validation of bioinformatics findings.
An investigation into the regulation of virulence factors by DNA supercoiling in gastrointestinal pathogens 16 Jul 2012
DNA supercoiling is a global regulator that plays a critical role in the regulation of virulence factors in many gastrointestinal pathogens including S. Typhimurium. Studies of Campylobacter jejuni have revealed that there is a strong correlation between DNA Supercoiling and the regulation of different virulence genes. However C. jejuni displays an absence of many of the classic regulators of virulence found in S.Typhimurium including nucleoid associated proteins. It has recently been demonstrated that DNA supercoiling affects the regulation of motility and invasion of epithelial cells by C.jejuni. The overall aim of this project is to investigate the regulation of virulence factors by DNA Supercoiling in these two key gastrointestinal pathogens. Transcriptional profiles will be generated for S.Typhimurium and C.jejuni by RNA-seq in response to changes in DNA topology. Bioinformatic analysis of these transcriptional profiles will lead to the identification of potential DNA supercoiling regulons as well as aid the design of predictive models for identifying genes in other pathogens which are regulated by changes in DNA topology. Finally in vitro infection assays will be used to validate and functionally characterise novel supercoiling regulons identified in this analysis.
Identification of novel antibiotics from bacteria using combined proteomics and computational approaches 24 Jun 2013
The aim of the project is to discover novel antibiotics from bacterial species, in particular from lactic acid bacteria (LAB) family. Lanthionine-containing antibiotic (lantibiotic) are a class of bacteriocins produced by LAB family that undergo post-translational modifications (PTMs). They have been widely used in the food safety and preservation industry (ex. Nisin) and possess potential biomedical applications. This project will involve Mass Spectrometry (MS) analyses in identification oflantibiotics from LAB species. Sample preparation for MS is a key step for a successful analysis, and two different analyses will be performed: (i) Unlabelled analysis and (ii) Labeling analysis using 2-mercaptoehtanol, sodiumborohydride and ethanethiol. MS analysis software, MaxQUANT, will be modified to incorporate lantibiotic associated modifications such as lanthionine, beta-methyl lanthionine, lysinoalanine, etc. Using genome mining on known lantibiotic associated genes, novel species of LAB will be predicted and analysed using MS. Lantibiotics purified from these species will be assessed
My overall goal is to understand why a synthetic lethal interaction observed in one individual may be absent in another, and to establish any rules that may be used to identify and prioritise those interactions most robust to genetic heterogeneity. My first key goal is to understand what factors might disrupt a given synthetic lethal interaction. I will assess this by using a reverse genetics approach to try to disrupt a well characterised interaction. My second key goal is to test wheth er robust synthetic lethal interactions can be identified by combining multiple screens from diverse cell lines. By focussing on the most widely screened oncogene, I will develop data integration methods that may be applicable to other mutations as the data associated with them increases. This will involve computational work followed by experimental validation. My final key goal is to find out whether certain categories of interactions, such as those between members of the same pathway, are m ore robust to changes in genetic background than others. Because experimental studies of individual genes or individual synthetic lethal interactions preclude the assessment of such trends, I will use computational modelling to assess a large number of synthetic lethal interactions across diverse backgrounds.
Discussing Professionalization, Gender, and Care: History of Soviet Healthcare in Comparative Perspective. 17 Dec 2013
This proposal is to fund a two-day workshop to evaluate Soviet nursing and healthcare history within a broader international context. To do this, it brings together scholars from the history of medicine, the history of nursing, and those working on the history of medicine in Russian studies. Russian nursing has only evolved in a western sense in the past twenty years and is still a developing profession. This workshop will therefore probe the complexities of Soviet nursing and healthcare h istory to yield greater insights into healthcare practices and attitudes in Russia and abroad. Should our understanding of Soviet nursing and healthcare conform to western notions of professional development? Does the Soviet case provide a new framework for interpreting healthcare history? The workshop will first examine Soviet nursing relative to international nursing and healthcare; and second, it will explore how nursing in the Soviet Union developed in relation to other medical profession s. Early career and established career scholars will have the opportunity to collaborate and comparatively assess Soviet nursing and healthcare. This workshop will be the first to focus on understanding the evolution of Russian nursing and healthcare more generally in a comparative context.
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
Toward a Phenomenology of the Anxious Body. 16 Sep 2013
The proposed activity consists of spending 3 months at the cole normale Sup rieure, Paris where the applicant will conduct research on anxiety from both a phenomenological and psychoanalytical perspective. Anxiety is the most common form of mental illness in the US and UK. Despite this, a rigorous analysis of anxiety at both an experiential and conceptual level remains overlooked. The project contributes to amending this oversight. Methodologically, the project uses an original methodology that combines a first-person perspective with psychoanalytical research. To achieve this aim, the applicant will collaborate with Professor Doroth e Legrand ( cole normale Sup rieure, Paris), who the applicant has a successful working history with. Legrand is a specialist in the intersection between psychoanalysis and phenomenology. This theme is essential to the project, and therefore to its success. The project involves three aspects: collaborative research; seminar presentations and parti cipation in ongoing specialist seminars on phenomenology and psychoanalysis at the ENS (all organised by Legrand); consolidation of research findings with publications aimed at both academic researchers and society at large. The impact of the project will be not only to deepen the understanding of anxiety, but also to enrich the clinical treatment of anxiety.