Structural basis of high-frequency horizontal gene transfer mediated by bacteriophage-like particles

Horizontal gene transfer (HGT) enables microbes to rapidly acquire novel genes such as those conferring antibiotic resistance. Virus-like particles called gene transfer agents (GTAs) mediate high-frequency HGT but remain largely unstudied. Understanding how GTAs recognise their hosts will allow us to assess their impact on environmental HGT and potential for biomedical applications such as gene delivery to the microbiome. I aim to characterise how the receptor-binding proteins of GTAs recognise their targets using a combination of structural methods, biochemical assays, and domain-exchange between two related producers of GTAs. Knowledge of how GTAs package bacterial genes is important for understanding the evolution of GTAs and informing the design of strategies to interfere with GTA-mediated HGT. I aim to describe this process in genetically distinct GTAs. I will employ an integrative approach combining molecular biology with cryo-electron tomography to visualise how GTAs assemble and what molecular machinery is involved in the process.