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Gregor Ebert

As seen in: Nature, Frontiers, Cell Host & Microbe, Cell Press
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Articles by Gregor Ebert

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies

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By Maren Kirstin Schuhmacher, Christoph Gruber, Christopher Lang, Ricardo M. W. Ruijpers, Lyupka Mazneykova, Brice Beinsteiner, Ariane Krus, Barbara Tremmel, Friederike Reinhardt, Karoline Kadletz, Zhe Ma, Lucie Casalta, Dina Y. Otify, Iolo Balken, Leon Hetzel, Juliane Merl-Pham, Tatjana Dorn, Marina Luchner, Lea Bauersachs, Karin Ganea, Natascha Wieser, Alexander Emrich, Emirhan Yağmur, Katrin Rager, Gauhar Sagindykova, Niklas Armbrust, Julian Geilenkeuser, Gil Westmeyer, Elvir Becirovic, Martin Biel, Rouzanna Istvanffy, Daniela M. Vogt Weisenhorn, Dong-Jiunn Jeffery Truong, Fabian J. Theis, Gregor Ebert, Alessandra Moretti, Ali Erturk, Andrea Bähr, Christian Kupatt, Marion Jasnin, Nikolai Klymiuk, Florian Giesert, Wolfgang Wurst
| Nature Verified
Abstract Evolution guides biological systems to populate ecological niches, with viruses among the most successful examples of this principle. Viruses evolved over billions of years to efficiently transfer genetic information. Although viruses are highly diverse, most have converged towards remarkable similarity in the size and shape of their capsids1,2. By contrast, generative models for protein design enable the creation of protein architectures that are absent from nature3,4,5.
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A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis

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By Svenja Lorenz Verified, Adam Wahida, Mark J. Bostock, Tobias Seibt, Anastasia Levkina, Dietrich Trümbach, Mohamed Soudy, David Emler, Nicola Rothammer, Marcel S. Woo, Jana K. Sonner, Mariia Novikova, Bernhard Henkelmann, Maceler Aldrovandi, Daniel F. Kaemena, Eikan Mishima, Perrine Vermonden, Zhi Zong, Deng Cheng, Toshitaka Nakamura, Junya Ito, Sebastian Doll, Bettina Proneth, Erika Bürkle, Francesca Rizzollo, Abril Escamilla Ayala, Valeria Napolitano, Marta Kolonko-Adamska, Stefan Gaussmann, Juliane Merl-Pham, Stefanie Hauck, Anna Pertek, Tanja Orschmann, Emily Van San, Tom Vanden Berghe, Daniela Hass, Adriano Maida, Joris M. Frenz, Lohans Pedrera, Amalia M. Dolga, Markus Kraiger, Helmut Fuchs, Gregor Ebert, Jerica Lenberg, Jennifer Friedman, Patrizia Agostinis, Annemarie Zimprich, Daniela Vogt-Weisenhorn, Lillian Garrett, Sabine M. Hölter, Wolfgang Wurst, Enrico Glaab, Jan Lewerenz, Bastian Popper, Christian Sieben Verified, Petra Steinacker, Hans Zischka, Ana J. García-Sáez, Anna Tietze, Sanath Kumar Ramesh, Scott Ayton, Michelle Vincendeau, Manuel A. Friese, Kristen Wigby, Michael Sattler, Matthias Mann, Irina Ingold, Ashok Kumar Jayavelu, Grzegorz M. Popowicz, Marcus Conrad
| Cell Press Verified
Keywords ferroptosis GPX4 Alzheimer’s disease neurodegeneration cell death neuroinflammation spondylometaphyseal dysplasia Sedaghatian type SSMD Introduction The progressive loss of neurons is a recurring feature of neurodegenerative diseases, a diverse group of disorders characterized by cognitive decline, motor impairment, and, in many cases, premature death.1,2,3,4 Although neuronal death is a shared endpoint, each neurodegenerative condition presents with distinct pathological hallmarks,...
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A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID - Nature Communications

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By Stefanie Bader, Dale J. Calleja, Shane Devine, Nathan W. Kuchel, Xinyu Wu, Richard W. Birkinshaw, Rohan Volpe, Liana Mackiewicz, Jan Schaefer, Elizabeth Kleeman, Gregor Ebert, Peter E. Czabotar, Anthony Hannan, Bernhard Lechtenberg, Melissa J. Call, Jeffrey Mitchell, Kym Lowes, Guillaume Lessene, Marcel Doerflinger
| Nature Verified
Abstract The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has highlighted the vulnerability of a globally connected population to zoonotic viruses. The FDA-approved coronavirus antiviral Paxlovid targets the essential SARS-CoV-2 main protease, Mpro.
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Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

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By Zhouyi Rong, Hongcheng Mai, Gregor Ebert, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Danilo Prtvar, Inderjeet Singh, Julia Schädler, Claire Delbridge, Hanno Steinke, Katja Schmidt, Christian J. Braun, Viktoria Ruf, Mayar Ali, Kurt-Wolfram Sühs, Mojtaba Nemati, Franziska Hopfner, Fatma Tritar Cherif, Zeynep Ilgin Kolabas, Muge MOLBAY, Izabela Horvath, Natalie Krahmer, Ali Önder Yildirim, Siegfried Ussar, Jochen Herms, Tobias B. Huber, Sabina Tahirovic, Nikolaus Plesnila, Gunter Hoglinger, Benjamin Ondruschka, Ingo Bechmann, Ulrike Protzer, Markus Elsner, Harsharan Singh Bhatia, Farida Hellal, Ali Erturk, Senbin Hu, Jinpeng Su, Hannah Frenzel, Gina Bruch, Selin Ulukaya, Denise Jeridi, Daniele Mistretta, Özüm Sehnaz Caliskan, Jochen Martin Wettengel, Susanne M. Schwarzmaier
| Cell Host & Microbe Verified
Keywords SARS-CoV-2 spike protein skull brain long COVID meninges mRNA vaccine neuroinflammation neurodegeneration tissue clearing Introduction SARS-CoV-2 infection is associated with numerous neurological complications1,2,3 and a heightened risk of ischemic strokes.4,5 Even mild cases of COVID-19 can result in long-term effects, including brain fogging and reduced gray matter thickness.6,7,8 While some studies detected SARS-CoV-2 in brain tissue,3,9,10,11,12 others did not,12,13,14,15,16...
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Multi-omics characterization of the monkeypox virus infection - Nature Communications

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By Yiqi Huang, Valter Bergant, Vincent Grass, M. Hamad, Julia Mergner, Karsten Krey, Rupert Öllinger, Till Bunse, Gregor Ebert, Florian Schmidt, Michael Way, Roland Rad, Andrew G. Bowie, Yonas M. Tesfamariam
| Nature Verified
Abstract Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay.
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Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections - Communications Biology

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By Sebastian Günther, Sven Falke, Julia Lieske, Jure Loboda, Alexander M. Herrmann, Aida Rahmani Mashhour, Aleksandra Usenik, Marcos Bryan Heinemann, Marcin Drag, Tobias Beck, Russell Cox, Henry Chapman, Christian Betzel, Gregor Ebert, Dusan Turk, Carsten Wrenger, Wiebke Ewert, Viviane Fongaro Botosso, Josana Kapronezai, Paula Roberta Giaretta, Winfried Hinrichs
| Nature Verified
Abstract Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2.
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A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation - Nature Communications

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By Katherine Martin, Victoria Jackson, Yanxiang Meng, Annette V. Jacobsen, Marcel Doerflinger, Christopher Horne, Matthew Cook, Vicki Athanasopoulos, Kate Lawlor, Ian Wicks, Gregor Ebert, Ashley P Ng, Jaclyn S. Pearson, André Samson, John Silke, James Murphy, Maria Kauppi
| Nature Verified
Abstract Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous inhibition of MLKL.
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The ubiquitylation of IL-1β limits its cleavage by caspase-1 and targets it for proteasomal degradation - Nature Communications

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By Rebecca Feltham, Zhengyang Liu, Gregor Ebert, Jaclyn S. Pearson, Laura F Dagley, James Murphy, Andrew Webb, Kate Lawlor, James Vince
| Nature Verified
Abstract Interleukin-1β (IL-1β) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in a variety of other inflammatory diseases. Therefore, IL-1β activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here, we show that precursor IL-1β is rapidly turned over by the proteasome and this correlates with its decoration by K11-linked, K63-linked and K48-linked ubiquitin chains.
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Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

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By Michael Vajdy, Srinivasa Reddy Bonam, Gregor Ebert
| Frontiers
Introduction The SARS-CoV-2 virus is a unclassified betacoronavirus with sequenced genomes ranging from 29.8 to 29.9 k RNA bases. The SARS-CoV-2 genome encodes replicase proteins, structural proteins, and accessory proteins (1). The ORF1a and ORF1ab polyproteins are proteolytically cleaved into 16 non-structural proteins designated nsp1-16 (1). Like SARS, COVID-19 manifests as a virulent zoonotic virus in humans with currently 101,211,750 global cases and 2,183,169 deaths as of Jan. 28, 2021 (2).
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Targeting the Extrinsic Pathway of Hepatocyte Apoptosis Promotes Clearance of Plasmodium Liver Infection

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By Sash Lopaticki, Matthew T. O’Neill, Gregor Ebert, Ryan W.J. Steel
| Cell Press Verified
Highlights • cIAPs are upregulated during Plasmodium liver infection • Inactivation of cIAPs preferentially kills liver-stage malaria parasites • IAP antagonists induce extrinsic apoptosis of infected hepatocytes and promote immunity • Targeting extrinsic apoptosis signaling could be a way to manage malaria infections Summary Plasmodium sporozoites infect the liver and develop into exoerythrocytic merozoites that initiate blood-stage disease.
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