By Edward Cunningham-Oakes
Making the decision to take a year out of academic study is never an easy one. Sure, there are a lot of benefits that come with doing an extra mural year, namely gaining a wealth of experience, and the freedom to not be confined within the boundaries of Guy’s Campus, which, whilst familiar can become excessively comfortable after spending too much time there. However, whilst deciding you consider the two major costs; firstly, there is the fear that you will become unable to settle back down into an academic routine upon your return, and secondly, you have to come to terms with the fact that all of your friends and colleagues you met following several awkward introductions and impromptu flat parties will have already graduated. I am happy however to say that none of these fears came to light, and that I have no regrets about my placement, nor could I ever expect what eventually came with it.
The start of my placement was a bit of a turbulent one. I started my first day at the Institute of Infection and Immunity under Dr. Yanmin Hu at St. George’s, armed with only a pad, a pen, and a vague knowledge of the underlying principles of the project. If I’m being completely honest, I was barely proficient with a Gilson pipette (sorry Dr Snape, no reflection on your teaching I promise!), but slowly I progressed and managed to expertly disguise myself as a competent bioscience student. My initial experiments were testing combination therapy in gram negative bacteria with the aim of increasing their susceptibility to well established antibiotic classes using adjunct agents. However, after speaking to Yanmin about using gram positives to provide a bit of variation to my daily routine, I was soon working methicillin sensitive and resistant Staphylococcus aureus (here in referred to as MSSA and MRSA respectively). This is where my project took an interesting turn.
As I was screening various compounds against a range of antibiotics, I consistently found a large amount of synergy (synergy referring to the ability of two drugs to work cooperatively in order to elicit an effect) between a compound at that time known as HT013006 (even I wasn’t told what the compound actually was), and aminoglycosides. The first technique I observed this synergy with was a fairly standard technique in microbiology known as the chequerboard technique. This technique utilises a 96-well plate in order to test the ability of 96 different combinations of different antibiotic concentrations(with one agent tested at a range of concentrations starting from a pre-specified value across the 12 columns of the plate, whilst the other agent is similarly tested from a pre-specified value down to a concentration of zero). From this technique, we observed a strong synergistic effect between the aminoglycosides gentamicin, tobramycin and neomycin against over 100 strains MRSA and MSSA. From here, we continued investigations using 24 hour time-kill experiments on agar, which used similar concentration combinations to those used in successful chequerboards. However, unlike chequerboard experiments time-kill examines the ability of antibiotic combinations to kill bacteria, rather than just inhibit their growth. Again, this produced positive results, which was ideal.
The most exciting part of the project was creating a formulation for the drug itself. The compound HT013006, which for the purposes of my project was revealed to be Nordihydroguaiaretic acid (NDGA), has been shown to have profound adverse system effects, such as renal and hepatotoxicity. However, this does not mean that it could not be used topically, as a large number of MRSA and MSSA infections are in fact afflictions of the skin. Indeed, experiments in vivo experiments using mice models showed that topical agents of combinations of NDGA with either neomycin, tobramycin or gentamicin all produced a profound decrease in the extent of staphylococcal skin infections following inoculation with either MRSA or MSSA. Eventually, I was fortunate enough to have this data go to publication.
To this day, I’m taken aback by how fast I went from being not quite so sure of myself in the lab to producing my own publication as primary author. I’m fortunate to have had a great supervisor, better colleagues in lab (special shout out to Caroline Moussa!), and just a bit of luck.
If I had one piece of advice to offer anyone considering the extra mural year, (or indeed any other opportunity in your life), it would be to just ride the waves as they come; you never know where it might take you, or what opportunities it might bring.
Edward is graduated with a BSc in Pharmacology in 2016 and was the President of KCL Biosciences Students’ Association in his final year. In previous years he has held the roles of Social Events Officer and Head of Operations on the committee.
He is now studying towards a PhD in Cardiff University.