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UbiProPox SIGNED

Modulation of the Ubiquitin Proteasome System During Multiple Stages of the Poxvirus Lifecycle

Total Cost €

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EC-Contrib. €

0

Partnership

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 UbiProPox project word cloud

Explore the words cloud of the UbiProPox project. It provides you a very rough idea of what is the project "UbiProPox" about.

ubiquitin    proteasomes    virology    valuable    multiple    lifecycle    modulate    indicated    coming    interactions    machinery    largely    capacities    viral    spatial    prototypic    unravel    function    virus    temporal    switch    assembly    degraded    complexity    ubiquitinated    proteins    uncoating    microscopy    repertoire    temporally    tools    context    unknown    poxviruses    regulate    viruses    replication    vaccinia    host    substrates    ub    circle    functions    genes    site    genome    cellular    requirement    mediated    cytoplasmic    advantage    mechanisms    sites    turn    majority    insights    uncover    biology    characterization    enveloped    virions    subset    progeny    packaged    differentially    core    reveal    degradative    modulates    proteasome    revealed    ligase    takes    explore    ascertain    cores    dna    forming    initiation    vacv    stages    cullin    cells    biochemistry    full    ubiquitination    serve    poxvirus    degradation    newly    molecular    cell   

Project "UbiProPox" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE LONDON 

Organization address
address: GOWER STREET
city: LONDON
postcode: WC1E 6BT
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙270˙000 €
 EC max contribution 2˙270˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON UK (LONDON) coordinator 2˙270˙000.00

Map

 Project objective

Vaccinia virus (VACV), the prototypic poxvirus, is a large, enveloped, DNA virus characterized by its cytoplasmic site of replication and large subset of genes. Due to the complexity of VACV, the majority of studies focus on the virus rather than the host cell. Thus the repertoire of cell factors and functions required for its replication remain largely unknown. Our previous work to define a subset of these, revealed the cellular degradation machinery as a key requirement of VACV replication. Our findings indicated that ubiquitin (Ub), Ub ligase activity, and proteasome-mediated degradation are required for multiple stages of the virus lifecycle. The aim of this proposal is to reveal how VACV differentially modulates or takes advantage of the Ub proteasome system during genome uncoating, the initiation of DNA replication, and the assembly of progeny virions. For genome uncoating we will characterize the spatial and temporal interactions between ubiquitinated viral proteins, proteasomes, the viral uncoating factor, and the viral genome that occur on cytoplasmic cores. To ascertain how Cullin-3 based ubiquitination and proteasome degradation facilitate the switch from uncoating to replication of the viral genome, we will identify the relevant Cullin-3 substrates in the context of a detailed characterization of viral replication initiation sites. Coming full circle, we will explore the mechanisms used by VACV to modulate cellular degradation such that ubiquitinated viral core proteins are packaged into newly forming virions without being degraded. Using systems biology, virology, cell biology, biochemistry, molecular biology and a wide range of microscopy approaches we will unravel the complex interactions between poxviruses and the host cell degradation machinery. In turn, as viruses often serve as valuable tools to study cell function, this work is likely to uncover new insights into how cells spatially and temporally regulate their own degradative capacities.

 Publications

year authors and title journal last update
List of publications.
2019 Daniel Fisch, Artur Yakimovich, Barbara Clough, Joseph Wright, Monique Bunyan, Michael Howell, Jason Mercer, Eva Frickel
Defining host–pathogen interactions employing an artificial intelligence workflow
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.40560
eLife 8 2020-04-24
2019 Corina Beerli, Artur Yakimovich, Samuel Kilcher, Glennys V. Reynoso, Gotthold Fläschner, Daniel J. Müller, Heather D. Hickman, Jason Mercer
Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility
published pages: 216-225, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0288-2
Nature Microbiology 4/2 2020-04-24
2019 Robert D. M. Gray, David Albrecht, Corina Beerli, Moona Huttunen, Gary H. Cohen, Ian J. White, Jemima J. Burden, Ricardo Henriques, Jason Mercer
Nanoscale polarization of the entry fusion complex of vaccinia virus drives efficient fusion
published pages: 1636-1644, ISSN: 2058-5276, DOI: 10.1038/s41564-019-0488-4
Nature Microbiology 4/10 2020-04-24
2019 Artur Yakimovich
mSphere of Influence: the Rise of Artificial Intelligence in Infection Biology
published pages: , ISSN: 2379-5042, DOI: 10.1128/mSphere.00315-19
mSphere 4/3 2020-04-24
2019 Pedro M. Pereira, David Albrecht, Siân Culley, Caron Jacobs, Mark Marsh, Jason Mercer, Ricardo Henriques
Fix Your Membrane Receptor Imaging: Actin Cytoskeleton and CD4 Membrane Organization Disruption by Chemical Fixation
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.00675
Frontiers in Immunology 10 2020-04-24
2019 Romain F Laine, Kalina L Tosheva, Nils Gustafsson, Robert D M Gray, Pedro Almada, David Albrecht, Gabriel T Risa, Fredrik Hurtig, Ann-Christin Lindås, Buzz Baum, Jason Mercer, Christophe Leterrier, Pedro M Pereira, Siân Culley, Ricardo Henriques
NanoJ: a high-performance open-source super-resolution microscopy toolbox
published pages: 163001, ISSN: 0022-3727, DOI: 10.1088/1361-6463/ab0261
Journal of Physics D: Applied Physics 52/16 2020-04-24
2018 Mercer, Jason; Leterrier, Christophe; Pereira, Pedro; Henriques, Ricardo; Culley, Siân; Albrecht, David; Jacobs, Caron
NanoJ-SQUIRREL: quantitative mapping and minimisation of super-resolution optical imaging artefacts
published pages: , ISSN: 1548-7091, DOI: 10.1101/158279
Nature Methods 15(4) 2020-04-01
2018 Karel Novy, Samuel Kilcher, Ulrich Omasits, Christopher Karl Ernst Bleck, Corina Beerli, Jakob Vowinckel, Caroline K. Martin, Mohammedyaseen Syedbasha, Alessio Maiolica, Ian White, Jason Mercer, Bernd Wollscheid
Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence
published pages: 588-599, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0142-6
Nature Microbiology 3/5 2020-04-01
2017 Robert D. M. Gray, Jason Mercer, Ricardo Henriques
Open-source Single-particle Analysis for Super-resolution Microscopy with VirusMapper
published pages: , ISSN: 1940-087X, DOI: 10.3791/55471
Journal of Visualized Experiments 122 2020-04-01
2017 Yakimovich, Artur; Huttunen, Moona; Zehnder, Benno; Coulter, Lesley J.; Gould, Victoria; Schneider, Christoph; Kopf, Manfred; McInnes, Colin J.; Greber, Urs F.; Mercer, Jason
Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives
published pages: , ISSN: 0022-538X, DOI: 10.3929/ethz-b-000177326
Journal of Virology 91(18) 2020-04-01
2016 Gray, Robert D.M.; Ricardo Henriques; Jerzy Samolej; Christopher Karl Ernst Bleck; Kathrin Maria Scherer; Pedro Matos Pereira; Corina Beerli; Jason Mercer
VirusMapper: open-source nanoscale mapping of viral architecture through super-resolution microscopy
published pages: , ISSN: 2045-2322, DOI: 10.1038/srep29132
Scientific Reports , 6 , Article 29132. (2016) 1 2020-04-01

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