-
Faculty of Arts and HumanitiesDean's Office, Faculty of Arts and HumanitiesJakobi 2, r 116-121 51005 Tartu linn, Tartu linn, Tartumaa EST0Institute of History and ArchaeologyJakobi 2 51005 Tartu linn, Tartu linn, Tartumaa EST0Institute of Estonian and General LinguisticsJakobi 2, IV korrus 51005 Tartu linn, Tartu linn, Tartumaa EST0Institute of Philosophy and SemioticsJakobi 2, III korrus, ruumid 302-337 51005 Tartu linn, Tartu linn, Tartumaa EST0Institute of Cultural ResearchÜlikooli 16 51003 Tartu linn, Tartu linn, Tartumaa EST0Institute of Foreign Languages and CulturesLossi 3 51003 Tartu linn, Tartu linn, Tartumaa EST0School of Theology and Religious StudiesÜlikooli 18 50090 Tartu linn, Tartu linn, Tartumaa EST0Viljandi Culture AcademyPosti 1 71004 Viljandi linn, Viljandimaa EST0Professors emeriti, Faculty of Arts and Humanities0Associate Professors emeriti, Faculty of Arts and Humanities0Faculty of Social SciencesDean's Office, Faculty of Social SciencesLossi 36 51003 Tartu linn, Tartu linn, Tartumaa EST0Institute of EducationJakobi 5 51005 Tartu linn, Tartu linn, Tartumaa EST0Johan Skytte Institute of Political StudiesLossi 36, ruum 301 51003 Tartu linn, Tartu linn, Tartumaa EST0School of Economics and Business AdministrationNarva mnt 18 51009 Tartu linn, Tartu linn, Tartumaa EST0Institute of PsychologyNäituse 2 50409 Tartu linn, Tartu linn, Tartumaa EST0School of LawNäituse 20 - 324 50409 Tartu linn, Tartu linn, Tartumaa EST0Institute of Social StudiesLossi 36 51003 Tartu linn, Tartu linn, Tartumaa EST0Narva CollegeRaekoja plats 2 20307 Narva linn, Ida-Virumaa EST0Pärnu CollegeRingi 35 80012 Pärnu linn, Pärnu linn, Pärnumaa EST0Professors emeriti, Faculty of Social Sciences0Associate Professors emeriti, Faculty of Social Sciences0Faculty of MedicineDean's Office, Faculty of MedicineRavila 19 50411 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Biomedicine and Translational MedicineBiomeedikum, Ravila 19 50411 Tartu linn, Tartu linn, Tartumaa ESTInstitute of PharmacyNooruse 1 50411 Tartu linn, Tartu linn, Tartumaa ESTInstitute of DentistryL. Puusepa 1a 50406 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Clinical MedicineL. Puusepa 8 50406 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Family Medicine and Public HealthRavila 19 50411 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Sport Sciences and PhysiotherapyUjula 4 51008 Tartu linn, Tartu linn, Tartumaa ESTProfessors emeriti, Faculty of Medicine0Associate Professors emeriti, Faculty of Medicine0Faculty of Science and TechnologyDean's Office, Faculty of Science and TechnologyVanemuise 46 - 208 51003 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Computer ScienceNarva mnt 18 51009 Tartu linn, Tartu linn, Tartumaa ESTInstitute of GenomicsRiia 23b/2 51010 Tartu linn, Tartu linn, Tartumaa ESTEstonian Marine Institute0Institute of PhysicsInstitute of ChemistryRavila 14a 50411 Tartu linn, Tartu linn, Tartumaa EST0Institute of Mathematics and StatisticsNarva mnt 18 51009 Tartu linn, Tartu linn, Tartumaa EST0Institute of Molecular and Cell BiologyRiia 23, 23b - 134 51010 Tartu linn, Tartu linn, Tartumaa ESTTartu ObservatoryObservatooriumi 1 61602 Tõravere alevik, Nõo vald, Tartumaa EST0Institute of TechnologyNooruse 1 50411 Tartu linn, Tartu linn, Tartumaa ESTInstitute of Ecology and Earth SciencesJ. Liivi tn 2 50409 Tartu linn, Tartu linn, Tartumaa ESTProfessors emeriti, Faculty of Science and Technology0Associate Professors emeriti, Faculty of Science and Technology0Institute of BioengineeringArea of Academic SecretaryHuman Resources OfficeUppsala 6, Lossi 36 51003 Tartu linn, Tartu linn, Tartumaa EST0Area of Head of FinanceFinance Office0Area of Director of AdministrationInformation Technology Office0Administrative OfficeÜlikooli 17 (III korrus) 51005 Tartu linn, Tartu linn, Tartumaa EST0Estates Office0Marketing and Communication OfficeÜlikooli 18, ruumid 102, 104, 209, 210 50090 Tartu linn, Tartu linn, Tartumaa EST0Area of Vice Rector for DevelopmentCentre for Entrepreneurship and InnovationNarva mnt 18 51009 Tartu linn, Tartu linn, Tartumaa EST0University of Tartu Natural History Museum and Botanical GardenVanemuise 46 51003 Tartu linn, Tartu linn, Tartumaa EST0International Cooperation and Protocol Office0University of Tartu MuseumLossi 25 51003 Tartu linn, Tartu linn, Tartumaa EST0Area of RectorRector's Strategy OfficeInternal Audit OfficeArea of Vice Rector for Academic AffairsOffice of Academic AffairsUniversity of Tartu Youth AcademyUppsala 10 51003 Tartu linn, Tartu linn, Tartumaa EST0Student Union OfficeÜlikooli 18b 51005 Tartu linn, Tartu linn, Tartumaa EST0Centre for Learning and TeachingArea of Vice Rector for ResearchUniversity of Tartu LibraryW. Struve 1 50091 Tartu linn, Tartu linn, Tartumaa EST0Grant Office
Doctoral defece: Sainan Wang „Structure-guided insights into the functions of CHIKV nsP2“
On February 19 at 2:15 p.m., Sainan Wang will defend her doctoral thesis in biomedical technology „Structure-guided insights into the functions of CHIKV nsP2“
Supervisor: Professor Andres Merits, University of Tartu
Opponent: Associate Professor Kenneth A. Stapleford, New York University Grossman School of Medicine, USA
Summary: Alphaviruses are enveloped viruses with positive-strand RNA genomes that are responsible for many human and animal diseases. One of the most medically important alphaviruses is chikungunya virus (CHIKV), which can cause chikungunya fever, an acute febrile disease typically accompanied by rash and debilitating and chronic arthralgia that can last for months or even years. Since its first massive outbreak at 2004, CHIKV has caused millions of cases in over 50 countries and has become a re-emerging pathogen of global importance. However, there are no licensed drugs to treat the disease caused by CHIKV infection.
Alphavirus genomic RNA replication depends on the process of RNA synthesis and modification carried out by non-structural proteins (nsPs) encoded by viral RNA. nsP2 is considered as the main driving force and master-regulator of RNA replication. However, the coordination of multiple enzymatic activities and other functions of nsP2 was poorly understood. The current study provided structural basis for better understanding of the roles of nsP2 in the alphavirus replication process; it also indicated that nsP2 can be engineered to perform additional functions required for virus replication. The main conclusions of this study could be illustrated as follows:
1: We identified the crucial residues that formed the stacking interactions between nsP2 and the RNA molecule corresponding to conserved 3’ end of CHIKV genome. Disruption of these interactions was found to have detrimental effect on viral RNA replication.
2: The flexible interdomain linker, connecting the N-terminal helicase and C-terminal protease regions of nsP2, was found to be essential for CHIKV replication as well; only small changes such as the deletion of one amino acid residue and the insertion of up to 10 amino acids residues were tolerated without significant impact on viral replication. However, the deletion of three or five residues of linker was lethal for CHIKV.
3: The insertion of G3BP/Rin binding motifs into the flexible regions of nsP2 (in the linker region or between different domains of nsP2 protease) was not only tolerated but the inserted sequence was able to support replication of mutant CHIKV in both mammalian and insect cells. The same insertion could also restore the infectivity of viruses lacking G3BP binding motifs in nsP3 in mammalian cells.
Defence can be followed in Zoom: https://ut-ee.zoom.us/j/9530588152?pwd=ZzgzMjY4YytzUkZ5aVRCd2pOdVNQQT09 (meeting ID: 953 058 8152, passcode: kaitsmine).