A5077652674- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Transgenic Plants and Applications
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Insect Resistance and Genetics
- RNA modifications and cancer
- Viral Infections and Immunology Research
- Protein purification and stability
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Bacteriophages and microbial interactions
- Mosquito-borne diseases and control
- interferon and immune responses
- Protein Structure and Dynamics
- Nuclear Structure and Function
- Microbial Fuel Cells and Bioremediation
- COVID-19 Clinical Research Studies
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Invertebrate Immune Response Mechanisms
- Force Microscopy Techniques and Applications
- Viral Infections and Vectors
- Electrocatalysts for Energy Conversion
Philips (United Kingdom)
2019-2022
European Molecular Biology Laboratory
2009-2020
Université Joseph Fourier
2009-2016
Université Grenoble Alpes
2011-2016
Centre National de la Recherche Scientifique
2009-2016
Unit of Virus Host Cell Interactions
2009-2016
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms that drive high infectivity, broad tissue tropism, and pathology. Our 2.85-angstrom cryo-electron microscopy structure of spike (S) glycoprotein reveals receptor binding domains tightly bind essential free fatty acid linoleic (LA) in three composite pockets. A similar pocket also appears...
As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)–binding pocket. FFA stabilizes locked conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind essential...
Abstract As the global burden of SARS-CoV-2 infections escalates, so does evolution viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts co-existing evolving differently in distinct cell types. The BriSΔ variant, originally identified as a subpopulation from isolate hCoV-19/England/02/2020, comprises spike an eight amino-acid deletion encompassing furin recognition...
Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrades mRNAs containing premature translation termination codons. Phosphorylation of the essential NMD effector UPF1 by phosphoinositide-3-kinase-like kinase (PIKK) SMG-1 key step in and occurs when SMG-1, its two regulatory factors SMG-8 SMG-9, form complex at terminating ribosome. Electron cryo-microscopy SMG-1–8–9-UPF1 shows head arm architecture characteristic PIKKs reveals different states...
Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. used cryo-electron microscopy at near-atomic resolution implemented novel, cost-effective, high-performance cloud computing reveal architectural features in...
Proteomics research revealed the impressive complexity of eukaryotic proteomes in unprecedented detail. It is now a commonly accepted notion that proteins cells mostly exist not as isolated entities but exert their biological activity association with many other proteins, humans ten or more, forming assembly lines cell for most if all vital functions.(1,2) Knowledge function and architecture these multiprotein assemblies requires provision superior quality sufficient quantity detailed...
Abstract The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists three subunits (PA, PB1 PB2) binds both highly conserved 3′- 5′-ends vRNA segment. is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced complexes define minimal human core complex. We show that PA-PB1...
Adenovirus-derived nanoparticles (ADDomer) comprise 60 copies of adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport, and deployment ADDomer-based therapeutics independent a cold chain. To expand scope ADDomers for new applications, we engineered ADDobodies, representing PBP crown domain, genetically separated from multimerization domain. We inserted heterologous sequences into hyper-variable loops, resulting in monomeric, thermostable ADDobodies...
We are witnessing tremendous advances in our understanding of the organization life. Complete genomes being deciphered with ever increasing speed and accuracy, thereby setting stage for addressing entire gene product repertoire cells, towards whole biological systems. Advances bioinformatics mass spectrometric techniques have revealed multitude interactions present proteome. Multiprotein complexes emerging as a paramount cornerstone activity, many proteins appear to participate, stably or...
Virus-like particles (VLPs) play a prominent role in vaccination as safe and highly versatile alternatives to attenuated or inactivated viruses subunit vaccines. We present here two innovations, VLP-factory™ ADDomer© , for creating VLPs displaying entire proteins peptide epitopes antigens, respectively, enable efficient vaccination. For producing these VLPs, we use MultiBac, baculovirus expression vector system (BEVS) that developed complex protein biologics insect cells transfected with an...
Abstract COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and pathology. Our cryo-EM structure of spike (S) glycoprotein reveals that receptor binding domains (RBDs) tightly specifically bind essential free fatty acid (FFA) linoleic (LA) in three composite pockets. The pocket also appears be present highly...
Proteomics research revealed the impressive complexity of eukaryotic proteomes in unprecedented detail. It is now a commonly accepted notion that proteins cells mostly exist not as isolated entities but exert their biological activity association with many other proteins, humans ten or more, forming assembly lines cell for most if all vital functions.1,2 Knowledge function and architecture these multiprotein assemblies requires provision superior quality sufficient quantity detailed...
Summary Adenovirus-derived dodecamer (ADDomer) nanoparticles comprise 60 copies of Adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport and deployment ADDomer-based therapeutics independent a cold-chain. To expand scope for new applications, we engineered ADDobodies. ADDobodies represent crown domain PBP, genetically separated from its multimerization domain. We inserted heterologous sequences into hyper-variable loops in The resulting were...
The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of E1E2 glycoproteins to bind on Aedes mosquito cells (ii) ability serum particles (HCVsp) replicate these cell lines. First, used purified expressing baculovirus-derived pseudo (bacHCVpp) so could investigate their with lines from aegypti (Aag-2) albopictus (C6/36). We initiated a series infections...
Abstract As the global burden of SARS-CoV-2 infections escalates, so does evolution viral variants which is particular concern due to their potential for increased transmissibility and pathology. In addition this entrenched variant diversity in circulation, RNA viruses can also display genetic within single infected hosts with co-existing evolving differently distinct cell types. The BriSΔ variant, originally identified as a subpopulation by passaging isolate hCoV-19/England/02/2020,...
Abstract As COVID-19 persists, severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor-binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA-binding stabilizes locked conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2 and VOCs bind...