Sophie Handson

• BSc (Hons) Biomedical Sciences
• Reverse genetic analysis of the bacterial helicase loader protein DnaI

DNA replication initiation is essential for genome duplication. During replication initiation all cells must load helicases at origins to facilitate DNA unwinding for DNA synthesis.  Despite the universal importance of helicase loading, crucial aspects of the process in bacteria are poorly understood. In particular the physiological relevance of a recently proposed interaction between the helicase loader protein and single-strand DNA, based on cryo-EM structures in vitro, is unclear. The goal of this proposal is to address this question in vivo using the genetically tractable model system of Bacillus subtilis. The approach employs new tools developed in the Murray lab that allow the construction and characterization of mutations within the essential helicase loaderprotein. This research project will extend our fundamental understanding of the bacterial DNA replication initiation mechanism and it will determine whether the proposed loader: ssDNA interface is a feasible target for drug development.

Funding source: Newcastle University

Project supervisor: Professor Heath Murray