I have been really lucky in the diversity of projects I have been able to work on before starting my PhD.
During my undergraduate degree (in biochemisty at the University of Leeds) I applied for a year long internship with Pfizer, working in their chemistry department on my own project looking to increasing the dissolution of poorly soluble compounds using an amorphous solid formulation. Unfortunately, about half way through the placement Pfizer decided to shut down their Cambridge site. This actually turned out to be a huge blessing (not only because we published the project) but because I also then got to work on a second project with MedImmune, developing an assay to detect early stage peptide aggregation in vitro using flourescent liposomes.
When I got back to Leeds, I then applied to do my final year project at St Jame’s Hospital, looking at microtubule dynamics in relation to neurodevelopment diseases. I really enjoyed working in such a multidisciplinary environment, and this motivated me to apply for a masters degree in ‘Interdisciplinary Biomedical Research’ at the University of Warwick.
At Warwick I graduated with the top mark in my cohort having completed modules in physics, chemistry, statistics, microscopy and, coding and systems biology. I also got the opportunity to work on two laboratory projects, one in structural microbiology, working in collaboration with Columbia University, and the other in polymer chemistry, which was subsequently published in ACS macromolecules.
I chose to apply for this PhD as I’m really interested in structural biology and understanding how biological activity is conferred by molecular geometry and composition, and because I get to try my hand at carbohydrate NMR!
The aim of my project is to explore the structure of the enterococcal polysaccharide antigen (EPA) and elucidate how the properties of this polymer modulate cell growth, division, and interactions with the host.
EPA is a rhamnose containing polysaccharide found on the cell surface of all Enterococci. The synthetic machinery of EPA can be split into two genetic loci; a conserved region (genes epaA-R) which is responsible for the construction of the EPA rhamnose containing backbone, and a variable region which is responsible for EPA backbone decoration. The decoration of EPA varies between strains and has been recently shown to play a critical role in cell growth and morphology, evasion of phagocytosis, and resistance against antibiotics in E. faecalis.
During my project I would like to determine the structure of the EPA backbone and decoration in a variety of strains using a combination of NMR and mass spectroscopy to understand strain to strain decoration variation and look at how EPA decoration confers biological activity. I also hope to investigate which EPA decorations are essential for virulence, resistance against antibiotics and normal cell growth and division to unravel the complexity of its multifaceted role in enterococcal biology.