EPFL BioE Talks SERIES "Zooming in on Coronavirus Replication Organelles"
Event details
| Date | 27.09.2021 |
| Hour | 16:00 › 17:00 |
| Speaker | Prof. Montserrat Bárcena, Leiden University Medical Center, Leiden (NL) |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
WEEKLY EPFL BIOE TALKS SERIES
Abstract:
Viruses are master manipulators of the cells and exploit cellular resources and pathways in a variety of ways. A striking example is the hijacking and remodeling of intracellular membranes by positive-strand RNA viruses, a group that includes notorious human pathogens like coronaviruses, enteroviruses or flaviviruses. The membrane structures induced by these viruses support the synthesis of viral RNA and are often referred to as viral replication organelles. Until recently, the structural characterization of viral replication organelles has been restricted to room-temperature EM samples. While these techniques provided a wealth of information about the architecture of these virus-induced membrane structures and the localization of molecular players, they have often raised key new questions. A paradigmatic example are the replication organelles of coronaviruses. Coronaviruses induce typical double-membrane vesicles (DMVs), inside which viral RNA synthesis is presumed to take place. Strikingly, coronaviral DMVs appeared to be closed compartments and therefore it was unclear how newly made viral RNA could be exported to the cytosol for translation and packaging into new virions. Cryo-EM and cellular cryotomography allowed us to revisit and analyze coronavirus-induced DMVs at macromolecular resolution. Our data unveiled a molecular pore complex spanning the two membranes of the DMVs that contains six copies of the largest viral transmembrane non-structural protein, nsp3, and could provide the long-sought gateway for viral RNA export. Additional work by our group and others suggests that viral oligomeric complexes controlling the traffic from/to viral replication organelles may well be a common theme across positive-strand RNA viruses. This new class of viral complexes offers novel targets for future antiviral interventions.
Bio:
Dr. Montse Bárcena is an Assistant Professor at the Section Electron Microscopy (EM) in the Department of Cell and Chemical Biology at the Leiden University Medical Center (LUMC) in The Netherlands. Imaging techniques have been a central tool in her research since the beginning of her career, when she investigated helicases by single particle analysis in the group of Prof. José María Carazo. After receiving her PhD in Madrid (Universidad Autónoma) and a stay in Prof. Teresa Ruiz’s lab at Vermont University as a Fulbright postdoctoral fellow, she joined the group of Prof. Bram Koster in The Netherlands with an EMBO (2003) and a Marie Curie fellowship (2005). Since then, she has been investigating viruses and viral infection. In 2010, she established her own group, which focuses on the replication of positive-strand RNA viruses like coronaviruses and picornaviruses. These viruses replicate on distinct membrane structures generated in the cytoplasm of the host cell during infection. These viral replication organelles are the working environment of the viral replication machinery and therefore the cradle for viral evolution. The Bárcena group aims at getting new insight into the poorly understood biogenesis, structure and function of these remarkable virus-induced structures, which could lead to novel antiviral strategies. Her lab uses a comprehensive multiscale and multimodal imaging approach, combining classic EM techniques with advanced methods like 3D-SEM, CLEM and cellular cryotomography.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
Abstract:
Viruses are master manipulators of the cells and exploit cellular resources and pathways in a variety of ways. A striking example is the hijacking and remodeling of intracellular membranes by positive-strand RNA viruses, a group that includes notorious human pathogens like coronaviruses, enteroviruses or flaviviruses. The membrane structures induced by these viruses support the synthesis of viral RNA and are often referred to as viral replication organelles. Until recently, the structural characterization of viral replication organelles has been restricted to room-temperature EM samples. While these techniques provided a wealth of information about the architecture of these virus-induced membrane structures and the localization of molecular players, they have often raised key new questions. A paradigmatic example are the replication organelles of coronaviruses. Coronaviruses induce typical double-membrane vesicles (DMVs), inside which viral RNA synthesis is presumed to take place. Strikingly, coronaviral DMVs appeared to be closed compartments and therefore it was unclear how newly made viral RNA could be exported to the cytosol for translation and packaging into new virions. Cryo-EM and cellular cryotomography allowed us to revisit and analyze coronavirus-induced DMVs at macromolecular resolution. Our data unveiled a molecular pore complex spanning the two membranes of the DMVs that contains six copies of the largest viral transmembrane non-structural protein, nsp3, and could provide the long-sought gateway for viral RNA export. Additional work by our group and others suggests that viral oligomeric complexes controlling the traffic from/to viral replication organelles may well be a common theme across positive-strand RNA viruses. This new class of viral complexes offers novel targets for future antiviral interventions.
Bio:
Dr. Montse Bárcena is an Assistant Professor at the Section Electron Microscopy (EM) in the Department of Cell and Chemical Biology at the Leiden University Medical Center (LUMC) in The Netherlands. Imaging techniques have been a central tool in her research since the beginning of her career, when she investigated helicases by single particle analysis in the group of Prof. José María Carazo. After receiving her PhD in Madrid (Universidad Autónoma) and a stay in Prof. Teresa Ruiz’s lab at Vermont University as a Fulbright postdoctoral fellow, she joined the group of Prof. Bram Koster in The Netherlands with an EMBO (2003) and a Marie Curie fellowship (2005). Since then, she has been investigating viruses and viral infection. In 2010, she established her own group, which focuses on the replication of positive-strand RNA viruses like coronaviruses and picornaviruses. These viruses replicate on distinct membrane structures generated in the cytoplasm of the host cell during infection. These viral replication organelles are the working environment of the viral replication machinery and therefore the cradle for viral evolution. The Bárcena group aims at getting new insight into the poorly understood biogenesis, structure and function of these remarkable virus-induced structures, which could lead to novel antiviral strategies. Her lab uses a comprehensive multiscale and multimodal imaging approach, combining classic EM techniques with advanced methods like 3D-SEM, CLEM and cellular cryotomography.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
Practical information
- Informed public
- Registration required
Organizer
- Prof. Gisou van der Goot, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD