Moving genes: structure and mechanism of serine recombinases involved in horizontal transfer of antimicrobial resistance
Supervisors:
Dr Martin Rennie, University of Glasgow
Dr Sean Colloms, University of Glasgow
Prof Helen Walden, University of Glasgow
CASE INDUSTRY PARTNER: Inspiralis Ltd, Norwich
Summary:
Site-specific recombinases are remarkable molecular machines that allow mobile genetic elements to integrate into and excise from bacterial chromosomes. These processes play important roles in bacteriophage lifecycles, bacterial genome evolution and the horizontal transfer of antibiotic resistance genes. Despite their importance, many recombinases associated with clinically relevant mobile elements remain poorly understood.
This project will investigate TnpX, a large serine recombinase responsible for mobilising the chloramphenicol resistance element Tn4451 from Clostridium perfringens. The student will combine bacterial genetics, molecular biology and biochemistry to determine how TnpX catalyses DNA recombination and how this process is regulated by a previously uncharacterised recombination directionality factor. Structural studies will investigate the role of novel DNA-binding domains present in TnpX but absent from well-studied bacteriophage integrases.
The student will receive multidisciplinary training in bacterial genetics, protein expression and purification, in vivo and in vitro recombination assays, protein-DNA interaction analysis, structural biology and cryo-electron microscopy. Through a CASE placement with Inspiralis Ltd., the student will also gain experience in industrial biotechnology, commercial protein production and the development of novel recombinase tools for synthetic biology and genome engineering. This unique combination of academic and industrial training will equip the student with a broad and highly transferable skillset for careers in both bioscience research and biotechnology.