High throughput genomic sequencing to understand the transmission and biology of human pathogens

Pathogen genetic sequencing is benefiting from improved laboratory workflows. COG-UK and the CARRIAGE study facilitate nation-wide acquisition and processing of SARS-CoV-2 and Staphylococcus aureus genomic data. I will utilise genomic and individual-level epidemiological data to understand the transmission and carriage dynamics. SARS-CoV-2 and Staphylococcus aureus are major human pathogens with significant disease burden. Importations of SARS- CoV-2 into the UK and transmission within University settings are considered sources of sustained SARS-CoV-2 spread and subject to restrictive measures, though poorly understood. S. aureus is an established pathogen in human populations and results in persistent nasal colonisation of approximately 25% of healthy people. Understanding the factors that result in transmission and colonisation of both pathogens, respectively, is vital to reduce subsequent disease. I will: 1) Characterise the contribution of imported SARS-CoV-2 to onwards transmission by coupling travel histories derived from Test and Trace to genetically linked clusters of infection. 2) Identify the transmission dynamics of SARS-CoV-2 by sequencing isolates derived through the University of Cambridge screening programme. 3) Characterise the microbial community structure that facilitates nasal Staphylococcus aureus carriage through microbiome analysis of 10,000 CARRIAGE study participants. 4) Experimentally validate genomic findings from microbiome data to identify pathways that facilitate S. aureus carriage