Innate immunity and viral spread are regulated by the SARS-CoV-2 papain-like protease
In early 2020, the outbreak of SARS-CoV-2 caused laboratories to close and scientists to work from home. With a view to tackling the virus, we joined forces with labs across Europe to contribute to the growing research on SARS-CoV-2. We focused on SARS-CoV-2 papain-like protease, PLpro, and compared it to previously characterised PLpro from SARS. PLpro can cleave small proteins such as ubiquitin or ISG15 from target proteins. We found that SARS-CoV-2 PLpro specifically cleaves ISG15 from its substrates, compared to SARS PLpro that specifically cleaves ubiquitin.
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Here we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of autophagy modifiers to autophagosomes. TBK1 phosphorylates LC3C and GABARAP-L2, which impedes LC3 binding to the processing enzyme ATG4.
https://doi.org/10.15252/embr.201948317
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Dr. Adriana Covarrubias
Adriana was born in La Serena, Chile. She obtained her Agronomic sciences degree at the University of La Serena. Her thesis was focused on the tolerance strategies under abiotic stress in Chenopodium quinoa. Adriana then decided to study a PhD in Cellular and Molecular Biology at the University Austral of Chile, Valdivia (Chile). Her research was dedicated in the Vitamin C homeostasis at the Central Nervous System and first focused on how ascorbic acid regulates the trafficking of SVCT2 transporter and second how the failure in the ascorbic acid homeostasis impaired the glucose uptake modulation in Huntington disease under the supervision of Dr. Maite A. Castro. In November 2017 Adriana joined the laboratory of Molecular Signaling of Prof. Dikic as a Postdoctoral researcher investigating the role of linear ubiquitination in the remodeling heart during myocardial infarct. Also, Adriana is currently studying novel mechanisms involved specifically in the regulation of ER-phagy.
Dr. Alexis Gonzalez
Dr. Andrea Gubaš
Anna Platzek
Anna gained first experience in the field of autophagy during her bachelor thesis in Anja Bremm’s lab. Since 2017 she is pursuing her Master in biochemistry at Goethe University in Frankfurt am Main and did a 6-month research internship in the lab of David Sabatini at Whitehead Institute in Cambridge, MA, where she investigated the mTOR pathway. For her master thesis she joined the lab of Ivan Dikic.
Dr. Anne-Claire Jacomin
Anne-Claire did her PhD in the lab of Marie-Odile Fauvarque (Université Grenoble-Alpes – France). Her work focused on the importance of ubiquitination in immune signaling and autophagy, with a specific interest in deubiquitinating enzymes. In 2014, she joined Ioannis Nezis at the University of Warwick – UK, for a postdoc aiming at deciphering the molecular mechanisms of selective autophagy in Drosophila. Since 2020, she joined the lab of Ivan Dikic and the Frankfurt Cancer Institute as a research assistant to work on the molecular mechanisms of tumor pathogenesis and the development of targeted therapies.
Anshu Bhattacharya
Antonia Hofmann
Dr. Chun Kew
Chun did his PhD in genetics at University of Cologne and Max Planck Institute for Biology of Ageing, Germany. He studied the effects of splicing factors on lifespan and innate immunity, under the supervision of Professor Adam Antebi. Chun joined Ivan’s laboratory in 2020. Now he is investigating the communications between extracellular bacteria and intracellular organelles of the host cells.
Dr. Cristian Prieto-Garcia
Cristian obtained his Veterinary medicine degree at the University of Cordoba and the University of Milan. During his degree he did a research internship at King's college London, where he investigated the role of GSK-3 in craniofacial development. After the internship, Cristian studied a Master's degree in Biochemistry, Molecular Biology and Biomedicine at the University Complutense of Madrid. He developed his Master's thesis at the CNIO, his thesis was focused on the function of KRAS at pre-neoplastic stages of Pancreatic Cancer. Then, Cristian did his PhD at Wuerzburg University. Under the supervision of Markus Diefenbacher, he revealed that USP28 deubiquitinates and stabilizes ΔNP63 to promote Squamous tumour formation. In June 2020, Cristian joined the lab of Ivan Dikic as a Postdoctoral researcher to study the role of ubiquitination in cancer using mouse models.
Diana Grewe
Dr. Donghyuk Shin
MD, Ines Tomašković
Prof. Ivan Dikic
Ivan Đikić is a leading expert in the fields of ubiquitin biology and cancer research. He is a professor at Goethe University Frankfurt and a fellow of Max Planck Society. He maintains the active research lab that enables multidisciplinary teams of scientists to study molecular principles of life and discovering pathological alterations that lead to the development of human diseases such as cancer, neurodegeneration and infection.
For his scientific work, Ivan received numerous awards, including the Ernst Jung Prize for Medicine and the Gottfried Wilhelm Leibniz Prize, the highest scientific honor in Germany. He is an elected member the EMBO, the German Academy Leopoldina and the European Academy, as well as an honorary member of the American Academy of Arts and Sciences. Ivan Đikić is committed to the education of the next generations of scientists globally. His efforts to popularize science in the public were recognized by the highest civilian state honors, The Order of Duke Branimir, bestowed by the President of Croatia.
Dr. Javier Garcia Pardo
Javier obtained both a degree in Biology and a degree in Biochemistry at the Autonomous University of Barcelona (UAB). He completed his PhD in Biochemistry, Molecular Biology and Biomedicine in 2015 in the group of Protein Engineering and Proteomics headed by Prof. FX Avilés at the IBB-UAB. Afterward, he continued his career as a postdoctoral scientist in the group of Prof. Daniel Ruiz-Molina lab at the Catalan Institute of Nanoscience and Nanotechnology (ICN2). He performed different visits to other research groups, such as the laboratory of Prof. Lloyd D. Fricker (AECOM, New York, USA) or the laboratory of Prof. Sir Tom Blundell (University of Cambridge, UK). He joined the Dikic lab in September 2018 and he is currently working with Reticulons, a group of ER-resident proteins involved in membrane curving. He is also investigating the structure and mechanism of human DNA-dependent metalloproteases and working in the discovery of new pharmacological targets for the NF-kB pathway.
Joel Kaufhold
Joel is a fourth year medical student. He has joined the lab in 2019 to study the role of selective autophagy in immune processes.
Dr. Lina Herhaus
After high school Lina obtained her first lab work experience in Mexico at the Research center ECOSUR. She then decided to study Applied Biology at the Hochschule Bonn-Rhein-Sieg (Germany) and Molecular Biology at the University of Dundee (UK) where she obtained a double degree with Honors. Lina performed her PhD studies at the MRC Protein Phosphorylation and Ubiquitylation Unit in Dundee under the supervision of Gopal Sapkota. Her dissertation focused on how deubiquitylating enzymes regulate the TGF-beta and BMP signaling pathways. Following her PhD studies, Lina received an EMBO fellowship for her postdoctoral research in the lab of Ivan Dikic to work on linear ubiquitylation and autophagy. After the postdoctoral work, she joined the Frankfurt Cancer Institute as a staff scientist of the cellular and biochemical analysis platform. Lina is now a team leader of the Immue Signaling program, which aims to decipher TBK1-mediated signaling in different pathologies.
Marcel Hahn
Dr. Marina Hoffmann
Dr. Mohit Misra
Philipp Busse
Philipp started studying Molecular Biosciences at the Goethe University in Frankfurt. After he finished his Bachelor’s degree he proceeded studying Biochemistry at the same University. He successfully did an internship in Lisbon focusing on biophysics and molecular interactions before he worked as a technician in the Paul-Ehrlich-Institute in the research group of Professor Hildt. In 2019 Philipp started working in the lab of professor Dikic as an intern, before he officially started his PhD project in the Buchmann Institute for Biosciences in the lab of professor Dikic.
Dr. Rukmini Mukherjee
Sara Ribicic
Originally from Split, Croatia Sara obtained her bachelor degree of Medical Laboratory Diagnostics with Honors at University of Split. She is currently obtaining her MSc diploma in Medicine with Industrial Specialization at Aalborg University, Denmark. She joined the lab in September 2019 for a year internship for her Master’s thesis project.
MD, Stefan Prgomet
Stefan studied medicine at the University of Zagreb, Croatia, where he obtained his MD studying the role of BMP 1-3 signaling in bone fracture healing. He continued his scientific interest by joining Ivan Dikic’s group in 2014 for 2 years, while he was focused on the characterization of the newly identified protein SPRTN and identified its essential role in DNA damage repair as a protease that cleaves DNA-protein-crosslinks. Subsequently he started his clinical and neurologic career first as a resident at the Clinic for Neurosurgery for 2 years and since 2019 at the Clinic for Neurology at the Goethe-University. He is in parallel continuing his scientific work at the Dr. Senckenberg Institute for Neurooncology and after achieving a fellowship from the Goethe-University Patenschaftsmodell he rejoined Ivan’s group 2020 to study the role of SPRTN and DNA-protein-crosslinks in brain tumors.
Dr. Varun Jayeshkumar Shah
Vigor Matkovic
Vigor was born in Rijeka, Croatia. After he finished high school in Opatija, he moved to Zagreb where he obtained his bachelor's degree in Chemistry at the Faculty of Science, University of Zagreb in summer 2016. Two years later he also defended the master thesis in Inorganic and Structural Chemistry at the Department of Chemistry, Faculty of Science, University of Zagreb, obtained the master's degree and two months later, in autumn 2018. he joined the lab of Ivan Dikic as a PhD student. During his PhD he is currently working on structural and biochemical identification of the effector proteins from Legionella pneumophila.
Yangxue Fu
Yaobin Liu
Dr. Yi-Lin Cheng
Yi-Lin obtained her Bachelor and Master degree in Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Taiwan. Afterwards, she received her PhD degree in Institute of Basic Medical Sciences, National Cheng Kung University, Taiwan in 2016. During her PhD research, she focused on the dengue virus-induced pathogenic inflammatory mediators through activating host transcription factors under the supervision of Dr. Yee-Shin Lin and Dr. Chiou-Feng Lin. Following this, she joined a cooperative project of group A streptococcus pathogenesis led by Dr. Jiunn-Jung Wu and Dr. Yee-Shin Lin as a postdoctoral fellow in Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taiwan. She studied on the mechanism of defective xenophagy of group A streptococcus in endothelial cells through regulation of galectins and ubiquitin as well as the induction of LC3-associated phagocytosis. With great interest in the autophagy field, Yi-Lin joined the Dikic’s lab as a postdoctoral researcher investigating the role of ER-phagy in Salmonella infection in September 2019.
for IBCII
Antonia Hofmann
Dikiclab manager at IBCII
Email: a.hofmann@med.uni-frankfurt.de
Fax: +49 (0) 69 6301 6602
Phone: +49 (0) 69 6301-83816
Antonia Hofmann
Dikiclab manager at IBCII
Email: a.hofmann@med.uni-frankfurt.de
Fax: +49 (0) 69 6301 6602
Phone: +49 (0) 69 6301-83816
for BMLS
Diana Grewe
Dikiclab manager at BMLS
Email: grewe@em.uni-frankfurt.de
Fax: +49 69 79876342581
Phone: +49 (0) 69 798-42581
Diana Grewe
Dikiclab manager at BMLS
Email: grewe@em.uni-frankfurt.de
Fax: +49 69 79876342581
Phone: +49 (0) 69 798-42581
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