The filamentous phage assembly system as a therapeutic tool (360G-Wellcome-210363_Z_18_Z)

Antibiotic resistance is a growing healthcare concern worldwide. The rise in the number of resistant bacteria is not being matched with an increase in new antibiotics or treatments. Novel ideas harnessing modern technology therefore need to be applied to address this problem in a timely manner. In this work, a phage encoded assembly system will be assessed for its potential application as a "switch" to control bacterial proliferation. By genetic manipulation of cells and viruses, protein expression, purification and high-end electron microscopy, the structure of a virus-encoded machinery in its host bacterial cell membrane will be determined in different conformational states. Furthermore, pilot experiments will be carried out to express and purify individual protein components for downstream mechanistic and high-resolution structural studies. The knowledge gained will provide many further avenues for research on our quest to develop advanced bactericides and synthetic cell-based treatments, and will deepen our understanding of bacterial pathogenicity in crops and animals, including humans. Funding for this proposal will also open up a multitude of downstream opportunities for collaboration with academia and industry, and importantly will provide me with the means to launch the crucial next stage of my career as an independent investigator.