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142 results on '"Goodbourn, Stephen"'

6. Viral immune modulators perturb the human molecular network by common and unique strategies

Author

Pichlmair, Andreas, Kandasamy, Kumaran, Alvisi, Gualtiero, Mulhern, Orla, Sacco, Roberto, Habjan, Matthias, Binder, Marco, Stefanovic, Adrijana, Eberle, Carol-Ann, Goncalves, Adriana, Bürckstümmer, Tilmann, Müller, André C., Fauster, Astrid, Holze, Cathleen, Lindsten, Kristina, Goodbourn, Stephen, Kochs, Georg, Weber, Friedemann, Bartenschlager, Ralf, Bowie, Andrew G., Bennett, Keiryn L., Colinge, Jacques, and Superti-Furga, Giulio

Published
2012
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16. Targeting pattern recognition receptors (PRR) for vaccine adjuvantation : from synthetic PRR agonists to the potential of Defective Interfering Particles (DIPs) of viruses

Author

Vasou, Andri, Sultanoglu , Nazife, Goodbourn, Stephen, Randall, Richard Edward, Kostrikis, Leondios G., The Wellcome Trust, University of St Andrews. School of Biology, and University of St Andrews. Biomedical Sciences Research Complex

Subjects
Innate immunity, QR355, QH301, SDG 3 - Good Health and Well-being, QH301 Biology, T-NDAS, Defective interfering particles, Defective viral genomes, Vaccine adjuvants, Pattern recognition receptor agonists, QR355 Virology
Abstract

This work was supported by financial support from the University of Cyprus (Grant 8037P-3/311-25020) awarded to L.G.K, and Wellcome Trust Senior Investigator Awards to S.G. and R.R. (101788/Z/13/Z, 101792/Z/13/Z). Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently developed adjuvants often include substances that stimulate pattern recognition receptors (PRRs), essential components of innate immunity required for the activation of antigen-presenting cells (APCs), which serve as a bridge between innate and adaptive immunity. Nearly all PRRs are potential targets for adjuvants. Given the recent success of toll-like receptor (TLR) agonists in vaccine development, molecules with similar, but additional, immunostimulatory activity, such as defective interfering particles (DIPs) of viruses, represent attractive candidates for vaccine adjuvants. This review outlines some of the recent advances in vaccine development related to the use of TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and discusses the potential applications of DIPs in vaccine adjuvantation. Publisher PDF

Published
2017

17. Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α)

Author

Giotis, Efstathios S., Robey, Rebecca C., Skinner, Natalie G., Tomlinson, Christopher D., Goodbourn, Stephen, Skinner, Michael A., and Biotechnology and Biological Sciences Research Council (BBSRC)

Subjects
[SDV]Life Sciences [q-bio], Interferon-alpha, Chick Embryo, Fibroblasts, Real-Time Polymerase Chain Reaction, Microbiology, veterinary(all), Genes, Animals, RNA, Veterinary Sciences, Chickens, Research Article, Oligonucleotide Array Sequence Analysis
Abstract

Viruses that infect birds pose major threats—to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3′-biased chicken microarray and a high density, “sense target”, whole transcriptome chicken microarray, with each recognising 120–150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies. Electronic supplementary material The online version of this article (doi:10.1186/s13567-016-0363-8) contains supplementary material, which is available to authorized users.

Published
2016
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18. MOESM1 of Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α)

Author

Giotis, Efstathios, Robey, Rebecca, Skinner, Natalie, Tomlinson, Christopher, Goodbourn, Stephen, and Skinner, Michael

Abstract

Additional file 1. Table of curated ChISGs identified by individual or multiple technologies. (1) An asterisk indicates a Gene ID not annotated in ENSEMBL. (2) Technologies identifying significant IRGs are listed as ‘1’ RNA-seq (using Kal’s Z test); ‘2’ Affymetrix 32K GeneChip Chicken Genome Array and ‘3’ Chicken Gene 1.0 ST Array’. ChISGs significant by one or both microarrays and RNA-seq using Kal’s Z test under relaxed criteria (FC > 2.5 or FDR

Published
2016
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22. Notch takes a short cut

Author

Goodbourn, Stephen

Subjects
Cell research -- Analysis, Genetic research -- Analysis, Cell differentiation -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A study shows that the classical signal-transduction pathway could be ignored totally by the events started by occupation of the Notch receptor. Study of the Notch gene is of great interest to biologists as the gene plays an important role in lateral specification, a process in which a cell differentiates. Cells in the ectodermal monolayer turn into neuronal-like tissue due to null mutations in Notch. A study is conducted on rats to understand the Notch signalling pathway.

Published
1995

49. Classical Swine Fever Virus Npro Antagonizes IRF3 To Prevent Interferon-Independent TLR3- and RIG-I-Mediated Apoptosis.

Author

Hardy, Samuel, Jackson, Ben, Goodbourn, Stephen, and Seago, Julian

Subjects
*AFRICAN swine fever, *CLASSICAL swine fever virus, *CLASSICAL swine fever, *BCL-2 proteins, *TYPE I interferons, *INTERFERON regulatory factors, *WILD boar
Abstract

Classical swine fever virus (CSFV) is the causative agent of classical swine fever, a notifiable disease of economic importance that causes severe leukopenia, fever, and hemorrhagic disease in domesticated pigs and wild boar across the globe. CSFV has been shown to antagonize the induction of type I interferon (IFN), partly through a function of its N-terminal protease (Npro), which binds interferon regulatory factor 3 (IRF3) and targets it for proteasomal degradation. Additionally, Npro has been shown to antagonize apoptosis triggered by the double-stranded RNA (dsRNA) homolog poly(I•C); however, the exact mechanism by which this is achieved has not been fully elucidated. In this study, we confirm the ability of Npro to inhibit dsRNA-mediated apoptosis and show that Npro is also able to antagonize Sendai virus (SeV)-mediated apoptosis in PK-15 cells. Gene-edited PK-15 cell lines were used to show the dsRNA-sensing pathogen recognition receptors (PRRs) TLR3 and RIG-I specifically respond to poly(I•C) and SeV, respectively, subsequently triggering apoptosis through pathways that converge on IRF3 and culminate in the cleavage of caspase-3. Importantly, this IRF3-mediated apoptosis was found to be dependent on transcription-independent functions of IRF3 and also on Bax, a proapoptotic Bcl-2 family protein, through a direct interaction between the two proteins. Deletion of IRF3, stable expression of Npro, and infection with wild-type CSFV were found to antagonize the mitochondrial localization of Bax, a key hallmark of the intrinsic, mitochondrial pathway of apoptosis. Together, these findings show that Npro's putative interaction with IRF3 is involved not only in its antagonism of type I IFN, but also dsRNA-mediated mitochondrial apoptosis. IMPORTANCE Responsible for severe hemorrhagic disease in domestic pigs and wild boar, classical swine fever is recognized by the World Organisation for Animal Health (OIE) and European Union as a notifiable disease of economic importance. Persistent infection, immunotolerance, and early dissemination of the virus at local sites of infection have been linked to the antagonism of type I IFN induction by Npro. This protein may further contribute to these phenomena by antagonizing the induction of dsRNA-mediated apoptosis. Ultimately, apoptosis is an important innate mechanism by which cells counter viruses at local sites of infection, thus preventing wider spread and dissemination within the host, potentially also contributing to the onset of persistence. Elucidation of the mechanism by which Npro antagonizes the apoptotic response will help inform the development of rationally designed live-attenuated vaccines and antivirals for control of outbreaks in typically CSFV-free countries. [ABSTRACT FROM AUTHOR]

Published
2021
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