Ub-BAC SIGNED
Dissecting and targeting ubiquitin networks in the course of bacterial infections
Total Cost €
0EC-Contrib. €
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Project "Ub-BAC" data sheet
The following table provides information about the project.
| Coordinator |
JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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 â€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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