简介
BRIEF SUMMARY OF RESEARCH INTERESTS AND ACHIEVEMENTS OF THE VIROLOGY GROUP
RNA viruses are the largest class of viruses and include many pathogens of humans and animals. As such, they are major cause of morbidity and mortality in humans and animals and are responsible for huge economic losses worldwide. Research of the Virology group addresses the molecular aspects of virus structure, entry, replication, assembly and spreading of human and animal RNA viruses, as well as host (innate) antiviral responses, pathogenesis, virus evolution and cross-species transmission, with emphasis on (emerging) corona , influenza, and picornaviruses. For this, a multidisciplinary approach entailing molecular virology (reverse and forward genetics), structural biology (crystallography, cryoEM), glycobiology, biophysics (e.g. BLI), biochemistry, cell biology (e.g. genetic screens), advanced light and electron microscopy, bio-informatics, and in vivo models is used.
In our studies towards virus structure, receptors and entry mechanisms, we have elucidated important insights into the structure, function and evolution of coronavirus spike proteins and influenza virus HA and NA proteins. Moreover, we identified several proteinaceous as well as glycan virus receptors and identified their importance for tropism and cross-species transmission, and we provided important new mechanistical insights in virus-cell attachment, endocytic uptake of virus particles, fusion between viral and host membranes, and viral genome release.
In our studies towards virus replication, we have revealed important new insights into how picornaviruses remodel intracellular signaling pathways and metabolic processes during infection for optimal replication and spreading. Furthermore, we have identified essential roles of picornavirus proteins and (hijacked) host factors in the formation and the architecture of viral replication organelles as well as in the process of viral RNA synthesis that takes place in these specialized compartments.
In our studies towards host innate antiviral responses, we have delivered new insights how cytosolic RNA sensors such as MDA5 and PKR signal to trigger innate IFN-α/β responses and stress responses to combat virus infection. We also provided important insights how viruses actively manipulate intracellular signaling pathways to suppress these antiviral responses; we revealed that picornavirus proteases cleave proteins involved in RLR signaling and stress granule formation, and we identified a novel class of viral stress antagonists with a novel mode of action.
Apart from obtaining fundamental knowledge, the Virology group aims to translate its knowledge into the development of new concepts for vaccines, antibodies, and antiviral drugs. Using recombinant proteins, multivalent epitope display on nanoparticles, virus-like particles, and live attenuated virus technologies, we have developed several innovative influenza and coronavirus vaccine candidates, several of which are currently explored by industrial partners for application. Moreover, we have identified several potent and broad-range inhibitors of enterovirus replication and elucidated their mode of action. Finally, we were the first to identify a human monoclonal antibody that can neutralize SARS-CoV-2.
BRIEF SUMMARY OF INTERNATIONAL VISIBILITY AND ACADEMIC ACTIVITIES
Publications: He has published >220 papers (of which > 90 in last 5 years) in peer-reviewed journals, of which several in high-impact journals such as Cell, Nature, Science, PNAS.
Grants: He obtained several grants from the Netherlands Organisation of Scientific Research (NWO), including prestigious personal grants (VIDI in 2003; VICI in 2011), consortium grants (NWO-TOP and ENW-Klein-2) and several other NWO grants (CW and ALW).
EU project coordination and participation: He has coordinated two Marie Curie European Training Networks on antiviral drug development (EUVIRNA, FP7, 2011-2015 and ANTIVIRALS, H2020, 2015-2019) and he is/was involved in several other EU networks (CARE, therapeutics against SARS-CoV-2; SCORE, antivirals against SARS-CoV-2; INITIATE, antiviral immunometabolism; OrganoVir, organoids for virus research; ENDFLU, influenza vaccines; ZAPI, zoonosis anticipation and preparedness initiative; SysVirDrug, broad-range antiviral drugs; SILVER, antivirals against emerging and neglected diseases).
Supervision: He has supervised >20 PhD students (and is currently guiding 10 PhD students) and >20 postdocs. He guided three of his postdocs to obtain NWO-VENI grants. Furthermore, he has guided postdocs (both incoming and outgoing) to obtain NWO-Rubicon, Marie Curie Fellowships and EMBO Fellowship grants.
Public Private Partnerships: He has obtained several multidisciplinary Public Private Partnership (PPP) grants from the Dutch Life Sciences and Health (LSH) Top Sector on vaccines, antibodies, and antiviral drug research together with industrial partners.
