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Ub-BAC SIGNED

Dissecting and targeting ubiquitin networks in the course of bacterial infections

Total Cost €

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EC-Contrib. €

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Partnership

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 Ub-BAC project word cloud

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

proteomics    despite    biology    strategies    eukaryotes    constitute    visualise    hypothesis    suitability    infections    setting    intracellular    activate    biomedical    clusters    phosphoproteome    dynamic    chemical    regulation    recruit    inhibitors    prokaryotes    cells    structural    chains    modifications    ligases    benefit    datasets    bacterial    pathogenicity    employ    ubiquitin    therapies    manipulate    ub    versatile    observation    global    exploited    proteome    medicinal    resolution    combination    virulence    translational    triggered    form    course    lacking    microscopy    modification    combatting    super    signalling    quantitative    community    facultative    nel    cell    contribution    salmonella    molecule    characterise    perform    host    gaining    single    holds    imaging    shigella    chemistry    focussed    ubiquitinome    unbiased    creates    cellular    epithelial    antibacterial    lines    resource    multiple    dissect    nanoscale    bacteria    fundamental    therapeutic    invaluable    macrophages    legionella    complexes    scientific    ubiquitination    infection    post   

Project "Ub-BAC" data sheet

The following table provides information about the project.

Coordinator
JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN 

Organization address
address: THEODOR W ADORNO PLATZ 1
city: FRANKFURT AM MAIN
postcode: 60323
website: www.uni-frankfurt.de

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 Germany [DE]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN DE (FRANKFURT AM MAIN) coordinator 2˙500˙000.00

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 Project objective

Ubiquitination represents one of the most versatile post-translational modifications in eukaryotes and is involved in regulation of numerous cellular processes. Despite prokaryotes lacking this system, facultative intracellular bacteria like Salmonella, Shigella and Legionella have evolved multiple strategies to manipulate the host ubiquitin (Ub) system to their own benefit. This proposal is focussed on gaining a fundamental understanding of the Ub system in the course of bacterial infections. We will employ advanced quantitative proteomics to perform a global analysis of the dynamic changes in the ubiquitinome and phosphoproteome of epithelial cells and macrophages upon infection with Salmonella, Shigella and Legionella. The comprehensive datasets will constitute an invaluable resource freely available to the scientific community. We expect to identify novel pathways triggered by selected bacterial ligases and will characterise their contribution to pathogenicity and virulence, as well as their suitability for being targeted in a therapeutic setting. Both medicinal chemistry and structural biology approaches will be exploited to identify inhibitors for NEL-type bacterial ligases. Hypothesis-driven projects within the work program focus on (i) a novel chemical modification of Ub controlling Legionella infections and (ii) the observation that Ub chains on Salmonella can form nanoscale clusters that recruit and activate multiple signalling pathways within the host cell. Super-resolution microscopy and single-molecule imaging will be used to visualise and dissect these Ub-triggered complexes. Taken together, the combination of unbiased global proteome analysis and hypothesis-driven projects creates a unique scientific program within the biomedical field of understanding and combatting bacterial infections. Along the same lines, this proposal holds a great potential for the future development of novel strategies for antibacterial therapies.

 Publications

year authors and title journal last update
List of publications.
2020 Donghyuk Shin, Rukmini Mukherjee, Yaobin Liu, Alexis Gonzalez, Florian Bonn, Yan Liu, Vladimir V. Rogov, Marcel Heinz, Alexandra Stolz, Gerhard Hummer, Volker Dötsch, Zhao-Qing Luo, Sagar Bhogaraju, Ivan Dikic
Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB
published pages: 164-179.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.10.019
Molecular Cell 77/1 2020-03-05
2018 Paolo Grumati, Ivan Dikic, Alexandra Stolz
ER-phagy at a glance
published pages: jcs217364, ISSN: 0021-9533, DOI: 10.1242/jcs.217364
Journal of Cell Science 131/17 2020-02-06
2018 Ivan Dikic, Zvulun Elazar
Mechanism and medical implications of mammalian autophagy
published pages: 349-364, ISSN: 1471-0072, DOI: 10.1038/s41580-018-0003-4
Nature Reviews Molecular Cell Biology 19/6 2020-02-06
2019 Christian Pohl, Ivan Dikic
Cellular quality control by the ubiquitin-proteasome system and autophagy
published pages: 818-822, ISSN: 0036-8075, DOI: 10.1126/science.aax3769
Science 366/6467 2020-02-06
2018 Alison Forrester, Chiara De Leonibus, Paolo Grumati, Elisa Fasana, Marilina Piemontese, Leopoldo Staiano, Ilaria Fregno, Andrea Raimondi, Alessandro Marazza, Gemma Bruno, Maria Iavazzo, Daniela Intartaglia, Marta Seczynska, Eelco Anken, Ivan Conte, Maria Antonietta De Matteis, Ivan Dikic, Maurizio Molinari, Carmine Settembre
A selective ER ‐phagy exerts procollagen quality control via a Calnexin‐ FAM 134B complex
published pages: , ISSN: 0261-4189, DOI: 10.15252/embj.201899847
The EMBO Journal 38/2 2020-02-06
2018 Lina Herhaus, Ivan Dikic
Dimerization quality control via ubiquitylation
published pages: 151-152, ISSN: 0036-8075, DOI: 10.1126/science.aav1391
Science 362/6411 2020-02-06
2019 Ramachandra M. Bhaskara, Paolo Grumati, Javier Garcia-Pardo, Sissy Kalayil, Adriana Covarrubias-Pinto, Wenbo Chen, Mikhail Kudryashev, Ivan Dikic, Gerhard Hummer
Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-10345-3
Nature Communications 10/1 2020-02-06
2019 Christian A. Hübner, Ivan Dikic
ER-phagy and human diseases
published pages: , ISSN: 1350-9047, DOI: 10.1038/s41418-019-0444-0
Cell Death & Differentiation 2020-02-06
2018 Ivan Dikic
Open questions: why should we care about ER-phagy and ER remodelling?
published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-018-0603-7
BMC Biology 16/1 2020-02-06
2019 Sagar Bhogaraju, Florian Bonn, Rukmini Mukherjee, Michael Adams, Moritz M. Pfleiderer, Wojciech P. Galej, Vigor Matkovic, Jaime Lopez-Mosqueda, Sissy Kalayil, Donghyuk Shin, Ivan Dikic
Inhibition of bacterial ubiquitin ligases by SidJ–calmodulin catalysed glutamylation
published pages: 382-386, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1440-8
Nature 572/7769 2020-02-06
2019 Kyoko E. Yuki, Hadir Marei, Evgenij Fiskin, Megan M. Eva, Angelica A. Gopal, Jeremy A. Schwartzentruber, Jacek Majewski, Mathieu Cellier, Judith N. Mandl, Silvia M. Vidal, Danielle Malo, Ivan Dikic
CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection
published pages: 1516-1531, ISSN: 2058-5276, DOI: 10.1038/s41564-019-0484-8
Nature Microbiology 4/9 2020-02-06
2018 Paolo Grumati, Ivan Dikic
Ubiquitin signaling and autophagy
published pages: 5404-5413, ISSN: 0021-9258, DOI: 10.1074/jbc.tm117.000117
Journal of Biological Chemistry 293/15 2020-02-06
2018 Sissy Kalayil, Sagar Bhogaraju, Florian Bonn, Donghyuk Shin, Yaobin Liu, Ninghai Gan, Jérôme Basquin, Paolo Grumati, Zhao-Qing Luo, Ivan Dikic
Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination
published pages: 734-738, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0145-8
Nature 557/7707 2019-10-08

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