Project description DEENESFRITPL Molecular events in herpes simplex virus type 1 replication Herpes simplex virus type 1 (HSV-1) is a widespread pathogen. However, the regulation of its genome replication is not well understood. The current model of HSV-1 genome replication includes an origin-dependent phase followed by an origin-independent phase. Funded by the Marie Skłodowska-Curie Actions programme, the HSV1_Single_Molecule project aims to elucidate molecular events of the less studied origin-independent replication phase using single-molecule imaging techniques. Previously, it was found that the HSV-1 origin binding protein UL9 is necessary for the origin-dependent but dispensable or inhibitory in the origin-independent phase. The research will focus on the role of UL9 as a switch factor from the first to the second phase and characterise in depth the conditions of UL9 binding to the origin of replication. Show the project objective Hide the project objective Objective Herpes simplex virus type 1 (HSV-1) is a widespread and well-known pathogen. However, we still lack a complete understanding of the mechanism of HSV-1 genome replication. We propose to revisit long-standing questions of the HSV-1 genome replication mechanism using cutting-edge single molecule imaging techniques. This approach enables the detection of transient structures and heterogeneous behavior, leading to further crucial insights into this fundamental process. The current model for HSV-1 genome replication comprises an origin-dependent followed by an origin-independent stage. Whereas we do have evidence and a good understanding of the origin-dependent phase, we completely lack evidence for the proposed structures of the origin-independent phase. Thus, in the proposed project we want to study aspects of the origin-dependent replication phase. Specifically, we want to reveal the role of the HSV-1 origin binding protein UL9 during replication as this protein was proposed to act as a switch from the first to the second stage. It has been shown that UL9 is an essential protein during the origin-dependent stage but dispensable and even inhibitory during the second, origin-independent stage. We here propose to use single-molecule imaging techniques to reveal the inhibitory effect of UL9 on HSV-1 mediated replication and to further characterize the specific conditions of UL9 binding to the origins of replication. Fields of science natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health scienceshealth sciencesinfectious diseasesDNA virusesnatural sciencesbiological sciencesgeneticsgenomes Keywords Herpes simplex virus type 1 HSV-1 single molecule imaging DNA replication Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Net EU contribution € 212 933,76 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 212 933,76