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Single molecule imaging of herpes simplex virus type 1 DNA replication

Project description

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.

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.

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

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76