Research

"Viruses largely impact on our agriculture and heath, and even control global-level environmental phenomena. Our group tackles on studying structure-functions of viruses that cause such problems."


1. Structural remnants of viruses in evolution. "Our challenge lies on exploring functional structural traits of viruses that threaten our health or harm our agriculture using a new approach." The protein folds of the capsid are conserved throughout the lineages of the viruses, demonstrating an evolutionary link among the viruses. Protozoan/fungal/algal viruses retain ansestoral structural features in unicellular hosts, while they have acquired multifunctionality in their capsid during evolution to ensure their proliferation in multicellular hosts including human. Hence, it is critical to clarify what functions are acquired through the evolution of icosahedral capsids by exploring what structural features are common and unique to a specific lineage of the virus. To investigate the acquired structure-functions of the icosahedral viruses, we have focused on representative cases of dsRNA, (+)ssRNA and ssDNA viruses; First, protozoan/fungal Totiviridae and metazoan totivirus-like dsRNA viruses. Second, algal picorna-like and invertebrate/vertabrate Picornavirales (+)ssRNA viruses. Third, algal ssDNA Bacilladnaviridae viruses and invertebrate/vertebrate ssRNA Nodaviridae viruses. Based on the structural analysis of these viruses, we have hypothesized newly acquired mechanisms with regards to extracellular transmission, genome transcription, and particle assembly/formation of these viruses.Left: Acquired functional structure of metazoan totivirus-like dsRNA viruses. Right: Structure-based phyrogenetic tree of (+)ssRNA algal picorna-like viruses and vertabrate/invertabrate/plant Picornavirales.

References: Okamoto et al., Acquired functional capsid structures in metazoan totivirus-like dsRNA viruses. Structure, (2020); Anna et al., Capsid structure of a marine algal virus of the order Picornavirales. J Virol (2020)


2. Life-and-death dynamics of algal blooms. "Our challenge lies on analyzing structure of host-specific algal viruses for revealing how they control harmful algal blooms." Algal blooms greatly impact the marine ecosystem, human activities such as fishery and seaside recreation, and human health. Monitoring of algal blooms is one of the important governmental programs for countries surrounded by the sea, including Sweden. Algal blooms show recurring patterns of sudden appearances and disappearances. A handful of host-specific algal viruses have been isolated from the marine algae that cause harmful algal blooms. The population of these host-specific algal viruses could control the disappearances and the appearances of the algal blooms. Hence, the host-specific algal viruses are key to understanding the life-and-death dynamics of the algal blooms. However, it is still unclear why these viruses are only infectious to certain algae. The capsid structure of these viruses are largely involved in the host-specific infection.Left: An atomic model of host-specific algal virus CtenRANVII. Right: Recurring patterns of seasonal algal blooms. 

References: Anna et al., Capsid structure of a marine algal virus of the order Picornavirales. J Virol (2020)


3. Large microassemblies in dogma-breaking giant viruses. "Our challenge lies on studying strucure-functions of microassemblies of the giant viruses, which will lead to elucidate their unique mechanisms concerning particle assembly and uncoating, cell entry and genome packaging." Our environment enriches giant amoeba/algal viruses, yet we know little about how they operate. The size of the giant viruses have often reached to the one of bacteria. They are tremendously unique and do not follow long-standing definition and criteria of viruses - witness of the fact that these viruses encode histone-like proteins, and transcriptional factors unlike other viruses. Therefore, they blur a boarderline between viruses and cellular organisms. Interestingly, our previous cryo-EM studies of Melbournevirus and the largest-ever Pithovirus sibericum have discovered mysterious surface and interior microassemblies in their particles. Cryo-EM images of A) Pithovirus sibericum B) Melbournevirus particles 

References: Okamoto et al., Cryo-EM structure of a Marseilleviridae virus particle reveals a large internal microassembly. Virology (2018); Okamoto et al., Structural variability and complexity of the giant Pithovirus sibericum particle revealed by high-voltage elecron cyro-tomography and energy-filgered electron cyro-microscopy. Sci Rep (2017)


4. COVID-19 pandemic action plan. Due to emergency needs this year, our group has kicked off studies on COVID-19 supported by KAW and SciLifeLab (official site) and is a part of a research area in high-throughput and high-content serology. Our main role is to establish a method on producing highly antigenic and bio-safe COVID-19 virus-like particle (VLP) for early serological diagnosis. The method will also permit to generate large-scale chimeric coronavirus VLPs that are applied for studying potential risk bat betacoronaviruses.