The six weeks I spent carrying out my research project in the Sir Patrick Dun Laboratory in Saint James’ Hospital was an unforgettable experience. I looked at the effects of a chemical compound termed L1 on Uropathogenic E. coli (UPEC), the main causative agent of urinary tract infections globally. I was interested in looking at the effects of L1 on UPEC as its inhibitory effects on the waaG enzyme had not been examined in live UPEC cells. WaaG is involved in synthesis of LPS, a component of the outer membrane enclosing UPEC bacterial cells that is important for the association of a protective capsule around UPEC cells. This capsule facilitates the survival of UPEC in the blood and plays a role in resistance to antibiotic treatments, so I wanted to examine the consequences of interfering with LPS synthesis and capsule association. Furthermore, I wanted to investigate the clinical implications this might have in terms of survival of UPEC in the blood and antibiotic susceptibility. I had the pleasure of working alongside Dr Naoise McGarry, who I cannot thank enough for supporting me throughout the project.
I began my research journey full of nervousness, unsure of what exactly to expect from the next few weeks ahead of me. Truthfully, my first day of research was overwhelming, serving as a complete shock to the system. I had made an exhaustive plan of the work I wanted to carry out and felt confident that while I had not carried out independent research before, I was ready to start. However, as soon as I stepped into the lab, this feeling of confidence swiftly vanished. The unfamiliar environment, the lab techniques to be learned, and the new responsibilities were intimidating and daunting. It was one thing making the plan, but another thing putting it into action. The first week or two proved to be an intense learning curve full of challenges I had not even anticipated. From developing the dexterity needed for the different lab techniques, to optimising my time in the lab, to keeping track of my results efficiently while in the lab and communicating with my supervisor, I certainly struggled and was pushed outside of the comfort zone that was my meticulous plan. This taught me that while planning is always important, being adaptable is a key part of research and indeed any project and is a vital transferable skill inevitably needed in all forms of leadership.
As I found my feet in the lab and started to see results, I began to enjoy the experience more and more. While some findings were unexpected and some experiments did not go to plan, this filled me with motivation and excitement of what else I might find as I continued my research. I also found that while I was working on my own in the lab for a large portion of the day, I was quite comfortable with this, which surprised me. I enjoyed methodically working through a protocol for a given experiment as it led to reliable results that I could stand by confidently. This was enlightening, as before the project I was unsure if I would find working alone in the lab isolating or not. Equally, I enjoyed regularly checking in and discussing my results with my supervisor and improved my capacity to collaborate and present information in a succinct manner. My research experience highlighted the benefits collaboration can have when working on a project, as discussing results and ideas with someone who shared a passion for my subject area was helpful for many reasons, such as getting to see a different point of view on a problem and learning more about a topic in which my expertise was lacking.
The results of my project are promising, and I hope to continue my work in this area in the future. I found that inhibition of waaG by L1 led to significantly decreased capsule association with UPEC cells, as well as a profound decrease in serum survival, and increased susceptibility to antibiotics. This suggests that there is a possibility of L1 being a potential drug candidate through collaboration with pharmacologists that could be used to prevent bloodstream infection and lower antibiotic doses used to treat infections, as well as reducing disturbance of the microbiome given the non-bactericidal nature of L1. My hope is that further investigations into the nature and effects of L1 could eventually lead to a dramatic reduction in the number of E. coli-related sepsis cases and serve as an innovative approach to counteracting antibiotic resistance!