Francesca Young

PhD thesis:

Auxiliary mobile genetic element-borne tRNA ligase as drivers of antimicrobial survival and adaptation in priority bacterial pathogens

Traditional approaches to the AMR crisis focus on identifying bacterial infections after they’ve acquired resistance genes, by which point, treatment options are already limited. As bacteria continuously evolve mechanisms to evade newly developed last-resort antibiotics, AMR may be more effectively addressed by targeting upstream, precursor biological mechanisms. Therefore, this project investigates a newly identified auxiliary tRNA ligase gene on a specific mobile genetic element, hypothesised to promote antibiotic tolerance and act as a “stepping stone” to antibiotic resistance. It has been linked to major diarrhoeal outbreaks and other major WHO concerns. This PhD aims to use functional microbiology approaches to characterise the mechanisms and evolutionary dynamics of these auxiliary tRNA ligases in vitro. Additionally, to establish their epidemiological relevance, the project aims to systematically screen global databases of successful AMR pathogen lineages to determine how widespread these precursor AMR signatures are. Collectively, these findings will fill research gaps in precursor AMR evolution and may encourage the development of proactive surveillance and earlier intervention.

Who or what inspired you to pursue your research interests?

At school, I was first inspired by a biology teacher whose enthusiasm and stories from his PhD in Genetics sparked my interest. I decided to pursue an integrated Master’s in Genetics at UCL, where my master's thesis on antimicrobial resistance in Prof Timothy McHugh’s microbiology laboratory consolidated my passion for microbial genetics. Having subsequently worked on a hospital ward for 6 months, witnessing first-hand the growing threat of AMR on patients, I became even more determined to make meaningful impacts in public health and infectious disease management through my research. Dr Kate Baker’s group represented the perfect environment to pursue this.