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Sexually transmitted infections are on the rise throughout the developed world, and this likely reflects changing behavioural and technological factors in a post-HIV world, resulting in a perfect epidemiological storm. However, many bacterial STIs are chronically understudied, with limited work being done to understand how these pathogens spread and evolve. In some cases this reflects an inability to efficiently culture the causative bacteria, making genomic and biological analysis challenging. At the Sanger Institute, we have been driving the development of direct sequencing approaches for the study of difficult to culture organisms such as Treponema pallidum, causative agent of syphilis, and are now applying this to large clinical cohorts of patients from around the world. In this talk, I will show how we are using these genomic tools to understand STI epidemiology and transmission dynamics, using examples from recent and ongoing syphilis and gonorrhoea studies.